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Maria Jos Rodríguez Francisca Herrera Wendy Donoso Ivn Castillo Roxana Orrego Daniel R. Gonzlez Jessica Zúiga-Hernndez 《International journal of molecular sciences》2020,21(22)
Liver fibrosis is a complex process associated to most types of chronic liver disease, which is characterized by a disturbance of hepatic tissue architecture and the excessive accumulation of extracellular matrix. Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor κB (NF-κB)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2–related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis. 相似文献
94.
Dr. Markella Konstantinidou Francesca Magari Fandi Sutanto Dr. Jörg Haupenthal Dr. Varsha R. Jumde Dr. M. Yagiz Ünver Prof. Dr. Andreas Heine Dr. Carlos Jamie Camacho Prof. Dr. Anna K. H. Hirsch Prof. Dr. Gerhard Klebe Prof. Dr. Alexander Dömling 《ChemMedChem》2020,15(8):680-684
Pharmacophore searches that include anchors, fragments contributing above average to receptor binding, combined with one-step syntheses are a powerful approach for the fast discovery of novel bioactive molecules. Here, we are presenting a pipeline for the rapid and efficient discovery of aspartyl protease inhibitors. First, we hypothesized that hydrazine could be a multi-valent warhead to interact with the active site Asp carboxylic acids. We incorporated the hydrazine anchor in a multicomponent reaction and created a large virtual library of hydrazine derivatives synthetically accessible in one-step. Next, we performed anchor-based pharmacophore screening of the libraries and resynthesized top-ranked compounds. The inhibitory potency of the molecules was finally assessed by an enzyme activity assay and the binding mode confirmed by several soaked crystal structures supporting the validity of the hypothesis and approach. The herein reported pipeline of tools will be of general value for the rapid generation of receptor binders beyond Asp proteases. 相似文献
95.
Nicki Frederiksen Assoc. Prof. Paul R. Hansen Dr. Dorota Zabicka Magdalena Tomczak Malgorzata Urbas Dr. Ilona Domraceva Prof. Fredrik Björkling Assoc. Prof. Henrik Franzyk 《ChemMedChem》2020,15(24):2544-2561
The influence of hydrophobicity on antibacterial activity versus the effect on the viability of mammalian cells for peptide/peptoid hybrids was examined for oligomers based on the cationic Lys-like peptoid residue combined with each of 28 hydrophobic amino acids in an alternating sequence. Their relative hydrophobicity was correlated to activity against both Gram-negative and Gram-positive species, human red blood cells, and HepG2 cells. This identified hydrophobic side chains that confer potent antibacterial activity (e. g., MICs of 2–8 μg/mL against E. coli) and low toxicity toward mammalian cells (<10 % hemolysis at 400 μg/mL and IC50>800 μg/mL for HepG2 viability). Most peptidomimetics retained activity against drug-resistant strains. These findings corroborate the hypothesis that for related peptidomimetics two hydrophobicity thresholds may be identified: i) it should exceed a certain level in order to confer antibacterial activity, and ii) there is an upper limit, beyond which cell selectivity is lost. It is envisioned that once identified for a given subclass of peptide-like antibacterials such thresholds can guide further optimisation. 相似文献
96.
Silicon - This study reports the effect of ageing on plasma polymerized hexamethyldisiloxane (pp-HMDSO) thin films properties during 90 days storage in the atmosphere. The monitoring of... 相似文献
97.
Makarov A. V. Savrai R. A. Skorynina P. A. Volkova E. G. 《Metal Science and Heat Treatment》2020,62(1-2):61-69
Metal Science and Heat Treatment - Results are provided for studying deformation methods of steel surface nanostructuring and hardening with martensitic, pearlitic and austenitic structures. A new... 相似文献
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99.
Larionov V. R. Lebedev M. P. Larionov A. S. 《Theoretical Foundations of Chemical Engineering》2018,52(4):686-689
Theoretical Foundations of Chemical Engineering - The prospects for extracting finely dispersed gold and other useful components from the magnetic tailings of gold recovery plants and other sources... 相似文献
100.
Z. M. Gizatullin M. G. Nuriev R. M. Gizatullin 《Journal of Communications Technology and Electronics》2018,63(1):87-93
For the action of a pulse field generated by industrial macrosources under the short-circuit condition used as an example, mathematical models, the circuit of an experimental setup, and design parameters for physical simulation of electromagnetic interferences in the communication lines of the electronic equipment have been proposed. The presented software provides the basis for a practical procedure for estimating the interference immunity of the electronic equipment subjected to the electromagnetic action of industrial macrosources. 相似文献