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41.
Shu CW Madiraju C Zhai D Welsh K Diaz P Sergienko E Sano R Reed JC 《Journal of biomolecular screening》2011,16(2):174-182
Autophagy is an evolutionarily conserved process for catabolizing damaged proteins and organelles in a lysosome-dependent manner. Dysregulation of autophagy may cause various diseases, such as cancer and neurodegeneration. However, the relevance of autophagy to diseases remains controversial because of the limited availability of chemical modulators. Herein, the authors developed a fluorescence-based assay for measuring activity of the autophagy protease, autophagin-1(Atg4B). The assay employs a novel reporter substrate of Atg4B composed of a natural substrate (LC3B) fused to an assayable enzyme (PLA(2)) that becomes active upon cleavage by this cysteine protease. A high-throughput screening (HTS) assay was validated with excellent Z' factor (>0.7), remaining robust for more than 5 h and suitable for screening of large chemical libraries. The HTS assay was validated by performing pilot screens with 2 small collections of compounds enriched in bioactive molecules (n = 1280 for Lopac? and 2000 for Spectrum? library), yielding confirmed hit rates of 0.23% and 0.70%, respectively. As counterscreens, PLA(2) and caspase-3 assays were employed to eliminate nonspecific inhibitors. In conclusion, the LC3B-PLA(2) reporter assay provides a platform for compound library screening for identification and characterization of Atg4B-specific inhibitors that may be useful as tools for interrogating the role of autophagy in disease models. 相似文献
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Inhibition of Trichoderma reesei cellulase by sugars (glucose, delta-gluconolactone, and cellobiose) and solvents (ethanol, butanol, and acetone) was studied using cellulose azure. Glucose, cellobiose, ethanol, and butanol were noncompetitive inhibitors, delta-gluconolactone was a mixed inhibitor, and acetone was a noncompetitive activator. Converting cellobiose to glucose reduces the effective inhibitor binding constant by 6 times and converting cellobiose to ethanol reduces it by 16 times. 相似文献
43.
Summary Polyurethane foam cubes were employed as carriers to immobilize Rhizopus oryzae for L(+)-lactic acid production. The immobilizing capacity reached 450 g-fresh cell/l-cube. The production rate of L(+)-lactic acid could be threefold increased by using the immobilized R. oryzae. The immobilized cells could be steadily used in repetitive fermentations for more than 10 batches. 相似文献
44.
水通道蛋白(Aquaporin,AQP)是一类选择性高效转运水分子的细胞膜通道蛋白,广泛存在于原核和真核生物细胞的细胞膜上,主要介导自由水分子的被动跨膜转运,对保持细胞内外液环境的稳态平衡起着重要的作用. 相似文献
45.
大气CO2浓度升高对稻季土壤中麦秸降解及氮素分趋的影响 总被引:1,自引:0,他引:1
利用中国唯一的稻麦轮作FACE(free-air carbon dioxide enrichment,开放式空气CO2浓度增高)试验平台,研究大气CO2浓度升高对稻季土壤中小麦秸秆降解速率及其氮素分趋的影响.试验设置Ambient(目前空气对照)和FACE(Ambient+200 μmol·mol-1)两个CO2浓度以及低氮处理(LN,150 kg·hm-2)和高氮处理(HN,250 kg·hm-2)两个氮肥水平,在稻季之初按标记麦秸/土壤重量比0.3%添加15N标记小麦秸秆,根据水稻生长时期依次采样测定秸秆降解速率,并通过分析土壤全氮、植株全氮及其15N丰度来观察已降解秸秆的氮素分趋情况.结果发现,大气CO2浓度升高对高氮处理土壤中小麦秸秆降解速率没有显著影响,但显著促进了低氮处理土壤中小麦秸秆的降解(p < 0.05),使其提高到与高氮处理土壤相当水平;大气CO2浓度升高显著增加了已降解秸秆中氮素的流失,在高氮处理土壤中尤为严重,而对植物吸收已降解秸秆中的氮素没有显著影响.结果表明,大气CO2浓度升高在土壤氮素相对不足时会加速土壤中小麦秸秆的降解,而在土壤氮素相对充足时又会加大降解秸秆中氮素的流失. 相似文献
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Concanavalin A (Con A)-induced hepatitis is thought to be a T-cell-mediated disease with active destruction of liver cells. Interleukin (IL)-17 is a cytokine produced principally by CD4(+) T cells. However, whether IL-17/IL-17 receptor (IL-17/IL-17R)-mediated responses are involved in T-cell-mediated Con A-induced liver injury remains unclear. In this study, we found that IL-17 expression was highly elevated in liver tissues during Con A-induced hepatitis. The increased levels of IL-17 were paralleled with the severity of liver injury reflected by Alanine aminotransaminase and histological assay as well as the secretion of tumor necrosis factor (TNF)-α and IL-6. Blockage of IL-17 significantly ameliorated Con A-induced hepatitis, while overexpression of IL-17 systemically resulted in massive hepatocyte necrosis in mice. Furthermore, overexpression of an IL-17R immunoglobulin G1 fusion protein significantly attenuated liver inflammation after acute Con A treatment. High expression of IL-17R on Kupffer cells was also observed along with the production of cytokines including TNF-α and IL-6. Inhibition of Kupffer cells by gadolinium chloride completely prevented Con A-induced liver injury and cytokine release. Finally, IL-17-expressing CD4(+) T and natural killer T cells were greatly increased in Con A-injected mice compared with that in controls. Overall, our results indicate that IL-17R signaling is critically involved in the pathogenesis in Con A-induced hepatitis, and blockade of IL-17/IL-17R signaling pathway may represent a novel therapeutic intervention in human autoimmune-related hepatitis. 相似文献
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50.
Hengdao Liu Hong Xiang Shaoli Zhao Haiqiang Sang Fenghua Lv Ruifang Chen Zhihao Shu Alex F. Chen Shuhua Chen Hongwei Lu 《Journal of cellular and molecular medicine》2019,23(2):798-810
The dipeptidyl peptidase 4 inhibitor vildagliptin (VLD), a widely used anti‐diabetic drug, exerts favourable effects on vascular endothelium in diabetes. We determined for the first time the improving effects of VLD on mitochondrial dysfunction in diabetic mice and human umbilical vein endothelial cells (HUVECs) cultured under hyperglycaemic conditions, and further explored the mechanism behind the anti‐diabetic activity. Mitochondrial ROS (mtROS) production was detected by fluorescent microscope and flow cytometry. Mitochondrial DNA damage and ATP synthesis were analysed by real time PCR and ATPlite assay, respectively. Mitochondrial network stained with MitoTracker Red to identify mitochondrial fragmentation was visualized under confocal microscopy. The expression levels of dynamin‐related proteins (Drp1 and Fis1) were determined by immunoblotting. We found that VLD significantly reduced mtROS production and mitochondrial DNA damage, but enhanced ATP synthesis in endothelium under diabetic conditions. Moreover, VLD reduced the expression of Drp1 and Fis1, blocked Drp1 translocation into mitochondria, and blunted mitochondrial fragmentation induced by hyperglycaemia. As a result, mitochondrial dysfunction was alleviated and mitochondrial morphology was restored by VLD. Additionally, VLD promoted the phosphorylation of AMPK and its target acetyl‐CoA carboxylase in the setting of high glucose, and AMPK activation led to a decreased expression and activation of Drp1. In conclusion, VLD improves endothelial mitochondrial dysfunction in diabetes, possibly through inhibiting Drp1‐mediated mitochondrial fission in an AMPK‐dependent manner. 相似文献