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11.
We investigate the complexity of preorder checking when the specification is a flat finite-state system whereas the implementation is either a non-flat finite-state system or a standard timed automaton. In both cases, we show that simulation checking is Exptime-hard, and for the case of a non-flat implementation, the result holds even if there is no synchronization between the parallel components and their alphabets of actions are pairwise disjoint. Moreover, we show that the considered problems become Pspace-complete when the specification is assumed to be deterministic. Additionally, we establish that comparing a synchronous non-flat system with no hiding and a flat system is Pspace-hard for any relation between trace containment and bisimulation equivalence, even if the flat system is assumed to be fixed. 相似文献
12.
Berger Seymour M.; Hampton Katherine L.; Carli Linda L.; Grandmaison Paul S.; Sadow Janice S.; Donath Clifford H.; Herschlag Laura R. 《Canadian Metallurgical Quarterly》1981,40(3):479
Three experiments with 204 undergraduates examined the hypothesis that an audience can inhibit overt practice and thereby impair learning of unfamiliar words and enhance learning of familiar words. This hypothesis was derived from an analysis of motoric and symbolic mediation during learning. In comparison with learning while alone, the results show that the audience inhibited overt practice of unfamiliar and familiar words and that reduced practice was detrimental to learning unfamiliar words. Inhibition of overt practice with an audience enhanced learning of familiar words in only 1 of the experiments. Instructions to practice overtly reduced the audience-inhibition effect in learning unfamiliar words. The studies are discussed in the context of drive-theory explanations for social facilitation effects in learning. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
13.
85 7–12 yr olds were asked to discuss happy, sad, or affectively neutral incidents that had been experienced either by themselves or by another child. Following the inducement of affect, the Ss were given the opportunity to share their experimental earnings with some less fortunate children. As predicted, a significant interaction of the discussion topic (self/other) and affect was found. Ss relating sad experiences encountered by another individual shared significantly more than those describing sad incidents that they had experienced. Although older Ss were more generous than the younger Ss in sharing their experimental earnings, age did not interact with the other experimental variables. (11 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
14.
Yilin Han Marianne King Evgenii Tikhomirov Povilas Barasa Cleide Dos Santos Souza Jonas Lindh Daiva Baltriukiene Laura Ferraiuolo Mimoun Azzouz Maurizio R. Gullo Elena N. Kozlova 《International journal of molecular sciences》2022,23(10)
Three-dimensional (3D) cultures, so-called organoids, have emerged as an attractive tool for disease modeling and therapeutic innovations. Here, we aim to determine if boundary cap neural crest stem cells (BC) can survive and differentiate in gelatin-based 3D bioprinted bioink scaffolds in order to establish an enabling technology for the fabrication of spinal cord organoids on a chip. BC previously demonstrated the ability to support survival and differentiation of co-implanted or co-cultured cells and supported motor neuron survival in excitotoxically challenged spinal cord slice cultures. We tested different combinations of bioink and cross-linked material, analyzed the survival of BC on the surface and inside the scaffolds, and then tested if human iPSC-derived neural cells (motor neuron precursors and astrocytes) can be printed with the same protocol, which was developed for BC. We showed that this protocol is applicable for human cells. Neural differentiation was more prominent in the peripheral compared to central parts of the printed construct, presumably because of easier access to differentiation-promoting factors in the medium. These findings show that the gelatin-based and enzymatically cross-linked hydrogel is a suitable bioink for building a multicellular, bioprinted spinal cord organoid, but that further measures are still required to achieve uniform neural differentiation. 相似文献
15.
Laura Mannarino Lara Paracchini Federica Pezzuto Gheorghe Emilian Olteanu Laura Moracci Luca Vedovelli Irene De Simone Cristina Bosetti Monica Lupi Rosy Amodeo Alessia Inglesi Maurizio Callari Serena Penpa Roberta Libener Sara Delfanti Antonina De Angelis Alberto Muzio Paolo Andrea Zucali Paola Allavena Giovanni Luca Ceresoli Sergio Marchini Fiorella Calabrese Maurizio DIncalci Federica Grosso 《International journal of molecular sciences》2022,23(10)
16.
Christabelle Rajesh Satish Sagar Ashok Kumar Rathinavel Divya Thomas Chemparathy Xianlu Laura Peng Jen Jen Yeh Michael A. Hollingsworth Prakash Radhakrishnan 《International journal of molecular sciences》2022,23(10)
Elevated levels of Mucin-16 (MUC16) in conjunction with a high expression of truncated O-glycans is implicated in playing crucial roles in the malignancy of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms by which such aberrant glycoforms present on MUC16 itself promote an increased disease burden in PDAC are yet to be elucidated. This study demonstrates that the CRISPR/Cas9-mediated genetic deletion of MUC16 in PDAC cells decreases tumor cell migration. We found that MUC16 enhances tumor malignancy by activating the integrin-linked kinase and focal adhesion kinase (ILK/FAK)-signaling axis. These findings are especially noteworthy in truncated O-glycan (Tn and STn antigen)-expressing PDAC cells. Activation of these oncogenic-signaling pathways resulted in part from interactions between MUC16 and integrin complexes (α4β1), which showed a stronger association with aberrant glycoforms of MUC16. Using a monoclonal antibody to functionally hinder MUC16 significantly reduced the migratory cascades in our model. Together, these findings suggest that truncated O-glycan containing MUC16 exacerbates malignancy in PDAC by activating FAK signaling through specific interactions with α4 and β1 integrin complexes on cancer cell membranes. Targeting these aberrant glycoforms of MUC16 can aid in the development of a novel platform to study and treat metastatic pancreatic cancer. 相似文献
17.
Ornella Rondinone Alessio Murgia Jole Costanza Silvia Tabano Margherita Camanni Luigi Corsaro Laura Fontana Patrizia Colapietro Luciano Calzari Silvia Motta Carlo Santaniello Tatjana Radaelli Enrico Ferrazzi Silvano Bosari Davide Gentilini Silvia Maria Sirchia Monica Miozzo 《International journal of molecular sciences》2022,23(10)
18.
Matteo Giovarelli Francesca Arnaboldi Silvia Zecchini Laura Brigida Cornaghi Ambra Nava Michele Sommariva Emilio Giuseppe Ignazio Clementi Nicoletta Gagliano 《International journal of molecular sciences》2022,23(15)
Duchenne muscular dystrophy (DMD) is a rare genetic disease leading to progressive muscle wasting, respiratory failure, and cardiomyopathy. Although muscle fibrosis represents a DMD hallmark, the organisation of the extracellular matrix and the molecular changes in its turnover are still not fully understood. To define the architectural changes over time in muscle fibrosis, we used an mdx mouse model of DMD and analysed collagen and glycosaminoglycans/proteoglycans content in skeletal muscle sections at different time points during disease progression and in comparison with age-matched controls. Collagen significantly increased particularly in the diaphragm, quadriceps, and gastrocnemius in adult mdx, with fibrosis significantly correlating with muscle degeneration. We also analysed collagen turnover pathways underlying fibrosis development in cultured primary quadriceps-derived fibroblasts. Collagen secretion and matrix metalloproteinases (MMPs) remained unaffected in both young and adult mdx compared to wt fibroblasts, whereas collagen cross-linking and tissue inhibitors of MMP (TIMP) expression significantly increased. We conclude that, in the DMD model we used, fibrosis mostly affects diaphragm and quadriceps with a higher collagen cross-linking and inhibition of MMPs that contribute differently to progressive collagen accumulation during fibrotic remodelling. This study offers a comprehensive histological and molecular characterisation of DMD-associated muscle fibrosis; it may thus provide new targets for tailored therapeutic interventions. 相似文献
19.
Bibiana C. Mota Nathan Ashburner Laura Abelleira-Hervas Liyueyue Liu Robertas Aleksynas Lucio Claudio Rovati Gianfranco Caselli Magdalena Sastre 《International journal of molecular sciences》2022,23(13)
Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer’s disease (AD). We recently demonstrated that the I2-ligand BU224 reversed memory impairments in AD transgenic mice and this effect was not because of reductions in amyloid-β (Aβ) deposition. In this study, our aim was to determine the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD, since this ligand has been proven to be safely tolerated in humans. Sub-chronic oral administration of CR4056 (30 mg/kg for 10 days) led to an improvement in recognition memory in 6-month-old 5xFAD mice, but not in wild-type littermates, without affecting Aβ levels or deposition. Our results also revealed a change in the profile of microglia by CR4056, resulting in a suppression of pro-inflammatory activated microglia, but increased the density of astrocytes and the expression of ApoE, which is mainly produced by these glial cells. In addition, CR4056 restored fibrinogen extravasation, affecting the distribution of markers of astrocytic end feet in blood vessels. Therefore, these results suggest that CR4056 protects against Aβ-mediated neuroinflammation and vascular damage, and offers therapeutic potential at any stage of AD. 相似文献
20.
Adelina Orellana Pablo García-Gonzlez Sergi Valero Laura Montrreal Itziar de Rojas Isabel Hernndez Maitee Rosende-Roca Liliana Vargas Juan Pablo Tartari Ester Esteban-De Antonio Urszula Bojaryn Leire Narvaiza Emilio Alarcn-Martín Montserrat Alegret Daniel Alcolea Alberto Lle Lluís Trraga Vanesa Pytel Amanda Cano Marta Marqui Merc Boada Agustín Ruiz 《International journal of molecular sciences》2022,23(13)
Background: Clinical diagnosis of Alzheimer’s disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST® ELISA and Lumipulse G® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer’s disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815−27). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects. 相似文献