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21.
Chiara Maria Motta Emanuela Califano Rosaria Scudiero Bice Avallone Chiara Fogliano Salvatore De Bonis Anja Raggio Palma Simoniello 《International journal of molecular sciences》2022,23(4)
In aquatic organisms, cadmium exposure occurs from ovum to death and the route of absorption is particularly wide, being represented by skin, gills and gastrointestinal tract, through which contaminated water and/or preys are ingested. It is known that cadmium interferes with the gut; however, less information is available on cadmium effects on an important component of the gut, namely goblet cells, specialized in mucus synthesis. In the present work, we studied the effects of two sublethal cadmium concentrations on the gut mucosa of Danio rerio. Particular attention was paid to changes in the distribution of glycan residues, and in metallothionein expression in intestinal cells. The results show that cadmium interferes with gut mucosa and goblet cells features. The effects are dose- and site-dependent, the anterior gut being more markedly affected than the midgut. Cadmium modifies the presence and/or distribution of glycans in the brush border and cytoplasm of enterocytes and in the goblet cells’ cytoplasm and alters the metallothionein expression and localization. The results suggest a significant interference of cadmium with mucosal efficiency, representing a health risk for the organism in direct contact with contamination and indirectly for the trophic chain. 相似文献
22.
Elvira Sondo Federico Cresta Cristina Pastorino Valeria Tomati Valeria Capurro Emanuela Pesce Mariateresa Lena Michele Iacomino Ave Maria Baffico Domenico Coviello Tiziano Bandiera Federico Zara Luis J. V. Galietta Renata Bocciardi Carlo Castellani Nicoletta Pedemonte 《International journal of molecular sciences》2022,23(6)
Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators. 相似文献
23.
Martina Fabris Fabio Del Ben Emanuela Sozio Antonio Paolo Beltrami Adriana Cif Giacomo Bertolino Federica Caponnetto Marco Cotrufo Carlo Tascini Francesco Curcio 《International journal of molecular sciences》2022,23(9)
The main aim of this study was to identify the most relevant cytokines which, when assessed in the earliest stages from hospital admission, may help to select COVID-19 patients with worse prognosis. A retrospective observational study was conducted in 415 COVID-19 patients (272 males; mean age 68 ± 14 years) hospitalized between May 2020 and March 2021. Within the first 72 h from hospital admission, patients were tested for a large panel of biomarkers, including C-reactive protein (CRP), Mid-regional proadrenomedullin (MR-proADM), Interferon-γ, interleukin 6 (IL-6), IL-1β, IL-8, IL-10, soluble IL2-receptor-α (sIL2Rα), IP10 and TNFα. Extensive statistical analyses were performed (correlations, t-tests, ranking tests and tree modeling). The mortality rate was 65/415 (15.7%) and a negative outcome (death and/or orotracheal intubation) affected 98/415 (23.6%) of cases. Univariate tests showed the majority of biomarkers increased in severe patients, but ranking tests helped to select the best variables to put on decisional tree modeling which identified IL-6 as the first dichotomic marker with a cut-off of 114 pg/mL. Then, a good synergy was found between IL-10, MR-proADM, sIL2Rα, IP10 and CRP in increasing the predictive value in classifying patients at risk or not for a negative outcome. In conclusion, beside IL-6, a panel of other cytokines representing the degree of immunoparalysis and the anti-inflammatory response (IP10, sIL2Rα and IL-10) showed synergic role when combined to biomarkers of systemic inflammation and endothelial dysfunction (CRP, MR-proADM) and may also better explain disease pathogenesis and suggests targeted intervention. 相似文献
24.
Dr. Alberto Dal Corso Margaux Frigoli Martina Prevosti Mattia Mason Dr. Raffaella Bucci Prof. Laura Belvisi Prof. Luca Pignataro Prof. Cesare Gennari 《ChemMedChem》2022,17(15):e202200279
Amine-carbamate self-immolative (SI) spacers represent practical and versatile tools in targeted prodrugs, but their slow degradation mechanism limits drug activation at the site of disease. We engineered a pyrrolidine-carbamate SI spacer with a tertiary amine handle which strongly accelerates the spacer cyclization to give a bicyclic urea and the free hydroxy groups of either cytotoxic (Camptothecin) or immunostimulatory (Resiquimod) drugs. In silico conformational analysis and pKa calculations suggest a plausible mechanism for the superior efficacy of the advanced SI spacer compared to state-of-art analogues. 相似文献
25.
Righi V Di Nunzio M Danesi F Schenetti L Mucci A Boschetti E Biagi P Bonora S Tugnoli V Bordoni A 《Lipids》2011,46(7):627-636
It is well recognized that a high dietary intake of long-chain polyunsaturated fatty acids (LC-PUFA) has profound benefits
on health and prevention of chronic diseases. In particular, in recent years there has been a dramatic surge of interest in
the health effects of n-3 LC-PUFA derived from fish, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Notwithstanding,
the metabolic fate and the effects of these fatty acids once inside the cell has seldom been comprehensively investigated.
Using cultured neonatal rat cardiomyocytes as model system we have investigated for the first time, by means of high-resolution
magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy in combination with gas chromatography (GC), the
modification occurring in the cell lipid environment after EPA and DHA supplementation. The most important difference between
control and n-3 LC-PUFA-supplemented cardiomyocytes highlighted by HR-MAS NMR spectroscopy is the increase of signals from
mobile lipids, identified as triacylglycerols (TAG). The observed increase of mobile TAG is a metabolic response to n-3 LC-PUFA
supplementation, which leads to an increased lipid storage. The sequestration of mobile lipids in lipid bodies provides a
deposit of stored energy that can be accessed in a regulated fashion according to metabolic need. Interestingly, while n-3
LC-PUFA supplementation to neonatal rat cardiomyocytes causes a huge variation in the cell lipid environment, it does not
induce detectable modifications in water-soluble metabolites, suggesting negligible interference with normal metabolic processes. 相似文献
26.
27.
Elisa Rumi Chiara Trotti Daniele Vanni Ilaria Carola Casetti Daniela Pietra Emanuela SantAntonio 《International journal of molecular sciences》2020,21(23)
Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have been well described, recent data has shed light on the complex and dynamic structure of PMF, that involves competing disease subclones, sequentially acquired genomic events, mostly in genes that are recurrently mutated in several myeloid neoplasms and in clonal hematopoiesis, and biological interactions between clonal hematopoietic stem cells and abnormal bone marrow niches. These observations may contribute to explain the wide heterogeneity in patients’ clinical presentation and prognosis, and support the recent effort to include molecular information in prognostic scoring systems used for therapeutic decision-making, leading to promising clinical translation. In this review, we aim to address the topic of PMF molecular genetics, focusing on four questions: (1) what is the role of mutations on disease pathogenesis? (2) what is their impact on patients’ clinical phenotype? (3) how do we integrate gene mutations in the risk stratification process? (4) how do we take advantage of molecular genetics when it comes to treatment decisions? 相似文献
28.
Arianna Giacomini Sara Taranto Sara Rezzola Sara Matarazzo Elisabetta Grillo Mattia Bugatti Alessia Scotuzzi Jessica Guerra Martina Di Trani Marco Presta Roberto Ronca 《International journal of molecular sciences》2020,21(24)
Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers. 相似文献
29.
Emanuela Tamburri Valeria Guglielmotti Silvia Orlanducci Maria Letizia Terranova Daniela Sordi Daniele Passeri Roberto Matassa Marco Rossi 《Polymer》2012,53(19):4045-4053
The detonation nanodiamond is a novel versatile nanomaterial with tunable properties and surface chemistry. In this work, we report on a template-free method to synthesize polyaniline based nanocomposite fibers during a chemical oxidative precipitation polymerization where the cooperative interactions between nanodiamond and polyaniline nucleates trigger the final morphology of the nanocomposite. FE–SEM and TEM observations evidence the prominent growth of fibril-like structures assembled in 2-D networks of tightly woven, partially oriented fibers. Optical and Raman spectroscopy and X-ray diffraction analyses reveal that the polymer chains are in a protonated emeraldine form and organize themselves in a highly ordered 3-D spatial arrangement. Conductivity measurements performed on isolated fibers by a conductive tip of an AFM apparatus highlight that the diamond filler does not affect the conductive properties of the polyaniline matrix while increases the thermal stability of the polymer as confirmed by TGA studies. 相似文献
30.
Sintering behavior of Ba/Sr celsian precursor obtained from zeolite‐A by ion‐exchange method 下载免费PDF全文
Mattia Biesuz Luca Spiridigliozzi Antonello Marocco Gianfranco Dell'Agli Vincenzo M. Sglavo Michele Pansini 《Journal of the American Ceramic Society》2017,100(12):5433-5443
(Ba, Sr)‐exchanged zeolite A with composition Ba0.74Sr0.22Na0.04Al2Si2O8 was prepared by cation exchange; a mild thermal treatment converts into an amorphous phase. Successive crystallization and sintering behavior was studied by XRD, DTA, and thermodilatometric analysis. The results point out the activation of viscous flow sintering mechanisms between 900°C and 1050°C. The densification process starts when the amorphous phase reaches its glass transition temperature (897°C) and finishes when the material crystallizes forming hexacelsian. The application of an external pressure in such temperature range allows to achieve an almost complete densification, the material transforming at 1300°C into dense monoclinic celsian much below the typical processing temperature. 相似文献