全文获取类型
收费全文 | 4721篇 |
免费 | 493篇 |
国内免费 | 459篇 |
专业分类
5673篇 |
出版年
2024年 | 10篇 |
2023年 | 56篇 |
2022年 | 129篇 |
2021年 | 201篇 |
2020年 | 161篇 |
2019年 | 244篇 |
2018年 | 193篇 |
2017年 | 179篇 |
2016年 | 205篇 |
2015年 | 295篇 |
2014年 | 305篇 |
2013年 | 347篇 |
2012年 | 386篇 |
2011年 | 349篇 |
2010年 | 249篇 |
2009年 | 220篇 |
2008年 | 231篇 |
2007年 | 208篇 |
2006年 | 177篇 |
2005年 | 163篇 |
2004年 | 175篇 |
2003年 | 198篇 |
2002年 | 227篇 |
2001年 | 136篇 |
2000年 | 117篇 |
1999年 | 91篇 |
1998年 | 81篇 |
1997年 | 60篇 |
1996年 | 37篇 |
1995年 | 32篇 |
1994年 | 23篇 |
1993年 | 16篇 |
1992年 | 14篇 |
1991年 | 26篇 |
1990年 | 20篇 |
1989年 | 24篇 |
1988年 | 10篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1979年 | 5篇 |
1973年 | 4篇 |
1966年 | 2篇 |
1959年 | 1篇 |
1948年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有5673条查询结果,搜索用时 8 毫秒
91.
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
92.
苦瓜的核糖体失活蛋白 总被引:6,自引:0,他引:6
核糖体失活蛋白是一类专一修饰核糖体的大亚基rRNA从而抑制蛋白质生物合成的蛋白毒素,可分为Ⅰ-型和Ⅱ-型两种类型。苦瓜中含有多种Ⅰ-型核糖体失活蛋白,如α-苦瓜素,β-苦瓜素和MAP30等,这些蛋白成分具有抗肿瘤、抗病毒和抗艾滋病等功能,因而近年来引起人们广泛的关注。对苦瓜核糖体失活蛋白的研究进展和应用前景进行了综述。 相似文献
93.
94.
95.
96.
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
97.
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
98.
目的考察胡桃楸提取液对肿瘤细胞Hela、K562的抑制作用和相关机制。方法用MTT方法分析胡桃楸提取液对Hela、K562细胞增殖的影响。采用端粒酶PCR ELISA试剂盒分析胡桃楸提取液对Hela、K562细胞端粒酶的影响。结果 Hela细胞24、48和72 h的LD50分别为406.18μg/mL、319.48μg/mL和112.84μg/mL。K562细胞24 h LD50为154.50μg/mL。HLF细胞LD50为918.69μg/mL。胡桃楸提取液可抑制Hela细胞和K562细胞的端粒酶活性,而对HLF细胞端粒酶活性影响不大。结论胡桃楸提取液对Hela细胞、K562细胞有抑制作用,在低浓度下对HLF细胞杀伤不大。对肿瘤细胞抑制作用可能与抑制端粒酶活性相关。 相似文献
99.
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
100.
目的:建立阿扎霉素B的分离与纯化工艺。方法:将阿扎霉素B的发酵液进行加热处理后,采用乙醇-乙酸乙酯的浸提系统,进行结晶、重结晶和柱层析制备。结果:发酵液经600℃热处理30min后,于室温条件下放置1d,阿扎霉素B的损失率仅为3.9%,阿扎霉素B经柱层析后,纯度达到98.1%,得率达到91.2%。结论:阿扎霉素B发酵液加热处理有利于过滤和离心,可延长发酵液在室温条件下的放置时间,提高阿扎霉素B的稳定性,乙醇-乙酸乙酯的浸提系统有利于提高阿扎霉素B的得率。 相似文献