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161.
Ana Beatriz Aguiar Sanford Leidivan Sousa da Cunha Caio Bezerra Machado Flvia Melo Cunha de Pinho Pessoa Abigail Nayara dos Santos Silva Rodrigo Monteiro Ribeiro Fabiano Cordeiro Moreira Manoel Odorico de Moraes Filho Maria Elisabete Amaral de Moraes Lucas Eduardo Botelho de Souza Andr Salim Khayat Caroline Aquino Moreira-Nunes 《International journal of molecular sciences》2022,23(15)
The circadian clock (CC) is a daily system that regulates the oscillations of physiological processes and can respond to the external environment in order to maintain internal homeostasis. For the functioning of the CC, the clock genes (CG) act in different metabolic pathways through the clock-controlled genes (CCG), providing cellular regulation. The CC’s interruption can result in the development of different diseases, such as neurodegenerative and metabolic disorders, as well as cancer. Leukemias correspond to a group of malignancies of the blood and bone marrow that occur when alterations in normal cellular regulatory processes cause the uncontrolled proliferation of hematopoietic stem cells. This review aimed to associate a deregulated CC with the manifestation of leukemia, looking for possible pathways involving CG and their possible role as leukemic biomarkers. 相似文献
162.
Eveline Santos da Silva Michel Kohnen Georges Gilson Therese Staub Victor Arendt Christiane Hilger Jean-Yves Servais Emilie Charpentier Olivia Domingues Chantal J. Snoeck Markus Ollert Carole Seguin-Devaux Danielle Perez-Bercoff 《International journal of molecular sciences》2022,23(14)
SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1. 相似文献
163.
Valentina Doldi Mara Lecchi Silva Ljevar Maurizio Colecchia Elisa Campi Giovanni Centonze Cristina Marenghi Tiziana Rancati Rosalba Miceli Paolo Verderio Riccardo Valdagni Paolo Gandellini Nadia Zaffaroni 《International journal of molecular sciences》2022,23(14)
Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients. 相似文献
164.
In this paper we describe a method for automatic extraction of main roads in high resolution aerial images. Because a road
may vary in color we aim at the detection of its centerline that is more uniform in color and shape. For this purpose, the
centerline is modeled as being a chain of short line segments. The method is based on an iterative process and is composed
by two stages: in the first stage seed segments are detected using the Radon transform. The second step is the automatic extraction
of the roads centerlines starting from the seeds that were found in the first stage. The Radon transform is again applied
to find the chain/series of segments candidates to centerline of main roads. In the final part of the paper we present experiments
using this approach and the results compared with a reference image. The accuracy of the automated method is evaluated considering
the completeness, correctness, and RMS indexes. 相似文献
165.
Performance of an Adaptive Controller for the Neuromuscular Blockade Based on Inversion of a Wiener Model 下载免费PDF全文
An adaptive controller based on a minimally parameterized parsimonious Wiener model for the effect of the muscle relaxant rocuronium in the neuromuscular blockade is presented. The controller structure combines inversion of the recursively identified static nonlinearity of the Wiener model with a positive compartmental control law for the linearized system. The overall strategy exploits the fact that the model has only two parameters, which are estimated by an extended Kalman filter. Due to the fact that the positive control law for total mass conservation of compartmental systems is only proven to be convergent for time‐invariant systems, the identification of the parameter in the linear block of the minimally parameterized parsimonious Wiener model is stopped when the controller is turned on. The controller was implemented in the platform Galeno and tested in simulation and in thirteen real cases of patients under general anesthesia. The good reference tracking results and robustness to noise show the reliability of the proposed strategy. 相似文献
166.
Inverse dynamic analysis is used in the study ofhuman gait to evaluate the reaction forces transmittedbetween adjacent anatomical segments and to calculate thenet moments-of-force that result from the muscle activityabout each biomechanical joint. The quality of theresults, in terms of reaction and muscle forces, is greatlyaffected not only by the choice of biomechanical model butalso by the kinematic data provided as input. This three-dimensional data is obtained through the reconstruction ofthe measured human motion. A biomechanical model isdeveloped representing human body components with acollection of rigid bodies interconnected by kinematicjoints. The data processing, leading to the spatialreconstruction of the anatomical point coordinates, usesfiltering techniques to eliminate the high frequencycomponents arising from the digitization process. Thetrajectory curves, describing the positions of theanatomical points are obtained using a form of polynomialinterpolation, generally cubic splines. The velocities andaccelerations are then the polynomial derivatives. Thisprocedure alone does not ensure that the kinematic data isconsistent with the biomechanical model adopted, becausethe underlying kinematic constraint equations are notnecessarily satisfied. In the present work, thereconstructed spatial positions of the anatomical pointsare corrected by ensuring that the kinematic constraints ofthe biomechanical model are not violated. The velocity andacceleration equations of the biomechanical model are thencalculated as the first and second time derivatives of theconstraint equations. The solution to these equationsprovides the model with kinematically consistent velocitiesand accelerations. The procedures are demonstrated throughthe application to a normal cadence stride period and theresults discussed with respect to the underlying principlesof the techniques used. 相似文献
167.
Grgoire B. Morand Isabel Cardona Sara Brito Silva Costa Cruz Alex M. Mlynarek Michael P. Hier Moulay A. Alaoui-Jamali Sabrina Daniela da Silva 《International journal of molecular sciences》2022,23(15)
The rise in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has prompted a quest for further understanding of the role of high-risk HPV in tumor initiation and progression. Patients with HPV-positive OPSCC (HPV+ OPSCC) have better prognoses than their HPV-negative counterparts; however, current therapeutic strategies for HPV+ OPSCC are overly aggressive and leave patients with life-long sequalae and poor quality of life. This highlights a need for customized treatment. Several clinical trials of treatment de-intensification to reduce acute and late toxicity without compromising efficacy have been conducted. This article reviews the differences and similarities in the pathogenesis and progression of HPV-related OPSCC compared to cervical cancer, with emphasis on the role of prophylactic and therapeutic vaccines as a potential de-intensification treatment strategy. Overall, the future development of novel and effective therapeutic agents for HPV-associated head and neck tumors promises to meet the challenges posed by this growing epidemic. 相似文献
168.
Sara Silva Kaido Kurrikoff Ülo Langel Antnio J. Almeida Nuno Vale 《International journal of molecular sciences》2022,23(15)
Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future. 相似文献
169.
Silva Khodjoyan Deborha Morissette Fortune Hontonnou Luis Checa Ruano Charles-Adrien Richard Olivier Sperandio Jean-Franois Elouët Marie Galloux Philippe Durand Stphanie Deville-Foillard Christina Sizun 《International journal of molecular sciences》2023,24(1)
The interaction between Respiratory Syncytial Virus phosphoprotein P and nucleoprotein N is essential for the formation of the holo RSV polymerase that carries out replication. In vitro screening of antivirals targeting the N-P protein interaction requires a molecular interaction model, ideally consisting of a complex between N protein and a short peptide corresponding to the C-terminal tail of the P protein. However, the flexibility of C-terminal P peptides as well as their phosphorylation status play a role in binding and may bias the outcome of an inhibition assay. We therefore investigated binding affinities and dynamics of this interaction by testing two N protein constructs and P peptides of different lengths and composition, using nuclear magnetic resonance and fluorescence polarization (FP). We show that, although the last C-terminal Phe241 residue is the main determinant for anchoring P to N, only longer peptides afford sub-micromolar affinity, despite increasing mobility towards the N-terminus. We investigated competitive binding by peptides and small compounds, including molecules used as fluorescent labels in FP. Based on these results, we draw optimized parameters for a robust RSV N-P inhibition assay and validated this assay with the M76 molecule, which displays antiviral properties, for further screening of chemical libraries. 相似文献
170.
Gabriel Alves Bonaf Jssica Silva dos Santos Jussara Vaz Ziegler Fernando Augusto Lima Marson Thalita Rocha Manoela Marques Ortega 《International journal of molecular sciences》2022,23(13)
Glycyrrhizic acid (GA), a natural compound isolated from licorice (Glycyrrhiza glabra), has exhibited anti-inflammatory and anti-tumor effects in vitro. Dipotassium glycyrrhizinate (DPG), a dipotassium salt of GA, also has shown an anti-tumor effect on glioblastoma cell lines, U87MG and T98G. The study investigated the DPG effects in the melanoma cell line (SK-MEL-28). MTT assay demonstrated that the viability of the cells was significantly decreased in a time- and dose-dependent manner after DPG (IC50 = 36 mM; 24 h). DNA fragmentation suggested that DPG (IC50) induced cellular apoptosis, which was confirmed by a significant number of TUNEL-positive cells (p-value = 0.048) and by PARP-1 [0.55 vs. 1.02 arbitrary units (AUs), p-value = 0.001], BAX (1.91 vs. 1.05 AUs, p-value = 0.09), and BCL-2 (0.51 vs. 1.07 AUs, p-value = 0.0018) mRNA compared to control cells. The proliferation and wound-healing assays showed an anti-proliferative effect on DPG-IC50-treated cells, also indicating an inhibitory effect on cell migration (p-values < 0.001). Moreover, it was observed that DPG promoted a 100% reduction in melanospheres formation (p-value = 0.008). Our previous microRNAs (miRs) global analysis has revealed that DPG might increase miR-4443 and miR-3620 expression levels. Thus, qPCR showed that after DPG treatment, SK-MEL-28 cells presented significantly high miR-4443 (1.77 vs. 1.04 AUs, p-value = 0.02) and miR-3620 (2.30 vs. 1.00 AUs, p-value = 0.01) expression compared to control cells, which are predicted to target the NF-kB, CD209 and TNC genes, respectively. Both genes are responsible for cell attachment and migration, and qPCR revealed significantly decreased CD209 (1.01 vs. 0.54 AUs, p-value = 0.018) and TNC (1.00 vs. 0.31 AUs, p-value = 2.38 × 10−6) mRNA expression levels after DPG compared to untreated cells. Furthermore, the migration of SK-MEL-28 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) was attenuated by adding DPG by wound-healing assay (48 h: p-value = 0.004; 72 h: p-value = 7.0 × 10−4). In addition, the MMP-9 expression level was inhibited by DPG in melanoma cells stimulated by TPA and compared to TPA-treated cells (3.56 vs. 0.99 AUs, p-value = 0.0016) after 24 h of treatment. Our results suggested that DPG has an apoptotic, anti-proliferative, and anti-migratory effect on SK-MEL-28 cells. DPG was also able to inhibit cancer stem-like cells that may cause cerebral tumor formation. 相似文献