全文获取类型
收费全文 | 2445篇 |
免费 | 164篇 |
国内免费 | 1篇 |
出版年
2023年 | 10篇 |
2022年 | 38篇 |
2021年 | 46篇 |
2020年 | 25篇 |
2019年 | 41篇 |
2018年 | 43篇 |
2017年 | 48篇 |
2016年 | 60篇 |
2015年 | 110篇 |
2014年 | 141篇 |
2013年 | 151篇 |
2012年 | 224篇 |
2011年 | 194篇 |
2010年 | 138篇 |
2009年 | 103篇 |
2008年 | 148篇 |
2007年 | 116篇 |
2006年 | 131篇 |
2005年 | 137篇 |
2004年 | 121篇 |
2003年 | 106篇 |
2002年 | 77篇 |
2001年 | 56篇 |
2000年 | 79篇 |
1999年 | 44篇 |
1998年 | 20篇 |
1997年 | 13篇 |
1996年 | 9篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 17篇 |
1992年 | 19篇 |
1991年 | 15篇 |
1990年 | 12篇 |
1989年 | 9篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 3篇 |
1980年 | 8篇 |
1979年 | 12篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1974年 | 2篇 |
1971年 | 2篇 |
1969年 | 2篇 |
排序方式: 共有2610条查询结果,搜索用时 15 毫秒
881.
882.
883.
Chimeric cytochromes P450 engineered by domain swapping and random mutagenesis for producing human metabolites of drugs
下载免费PDF全文
![点击此处可从《Biotechnology and bioengineering》网站下载免费的PDF全文](/ch/ext_images/free.gif)
884.
We hypothesized that C-reactive protein (CRP) may affect the cell cycle and induce apoptotic changes of monocytes. CRP (∼25 μg/ml) significantly increased expressions of B-cell translocation gene 2 (BTG2) mRNA and protein in human monocytes through pathways involving CD32/NADPH oxidase 2/p53, which eventually induced G2/M phase arrest and apoptotic cell death. Such pro-apoptotic effect of CRP was not found in thioglycollate-elicited intraperitoneal monocytes/macrophages harvested from BTG2-knockout male C57BL/6 mice (n = 5). Within atheromatous plaques obtained from CRP-transgenic male LDLR−/− C57BL/6 mice (n = 5) and human coronary arteries, BTG2 co-localized with CRP, p53 and monocytes/macrophages. Therefore the pro-apoptotic pathway of CRP-CD32-Nox2-p53-BTG2 may contribute to the retardation of the atherogenic process. 相似文献
885.
886.
887.
888.
A large set of mutants of CYP102A1 from Bacillus megaterium have human cytochrome P450-like activities and the ability to metabolize a number of marketed drugs and steroids. Here, we tested whether the CYP102A1 mutants could be used to produce hydroxylated human metabolites of 17β-estradiol (E2). A set of the mutants, which were generated by site-directed and random mutagenesis, was used to produce hydroxylated human metabolites of E2 in this study. Some of the tested mutants could regioselectively generate 2-OH E2 as a major metabolite but not other hydroxylated products. These results suggest that CYP102A1 mutants would be useful for the bioconversion of steroid hormones to hydroxylated products, which can be used for industrial applications. 相似文献
889.
Yongfeng He Hangun Kim Taeyong Ryu Kwang-Youl Lee Won-Seok Choi Kyeong-Man Kim Mei Zheng Yechan Joh Jae-Hyuk Lee Dong-Deuk Kwon Qun Lu Kwonseop Kim 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2014
Although δ-catenin was first considered as a brain specific protein, strong evidence of δ-catenin overexpression in various cancers, including prostate cancer, has been accumulated. Phosphorylation of δ-catenin by Akt and GSK3β has been studied in various cell lines. However, tyrosine phosphorylation of δ-catenin in prostate cancer cells remains unknown. In the current study, we demonstrated that Src kinase itself phosphorylates δ-catenin on its tyrosine residues in prostate cancer cells and further illustrated that Y1073, Y1112 and Y1176 of δ-catenin are predominant sites responsible for tyrosine phosphorylation mediated by c-Src. Apart from c-Src, other Src family kinases, including Fgr, Fyn and Lyn, can also phosphorylate δ-catenin. We also found that c-Src-mediated Tyr-phosphorylation of δ-catenin increases its stability via decreasing its affinity to GSK3β and enhances its ability of inducing nuclear distribution of β-catenin through interrupting the integrity of the E-cadherin. Taken together, these results indicate that c-Src can enhance the oncogenic function of δ-catenin in prostate cancer cells. 相似文献
890.
Jihye Ryu Minkyung Kang Mi-Sook Lee Hye-Jin Kim Seo Hee Nam Haeng Eun Song Doohyung Lee Jung Weon Lee 《Molecular and cellular biology》2014,34(16):2946-2960
TM4SF5 overexpressed in hepatocellular carcinoma activates focal adhesion kinase (FAK) during tumor cell migration. However, it remains unknown how TM4SF5 in hepatocellular carcinoma cells compromises with immune actions initiated by extracellular cytokines. Normal and cancerous hepatocytes with or without TM4SF5 expression were analyzed for the effects of cytokine signaling activity on TM4SF5/FAK signaling and metastatic potential. We found that interleukin-6 (IL-6) was differentially expressed in hepatocytes depending on cancerous malignancy and TM4SF5 expression. IL-6 treatment activated FAK and STAT3 and enhanced focal adhesion (FA) formation in TM4SF5-null cells, but it decreased TM4SF5-dependent FAK activity and FA formation in SNU761-TM4SF5 cells. STAT3 suppression abolished the IL-6-mediated effects in normal Chang cells, but it did not recover the TM4SF5-dependent FAK activity that was inhibited by IL-6 treatment in cancerous SNU761-TM4SF5 cells. In addition, modulation of FAK activity did not change the IL-6-mediated STAT3 activity in either the Chang or SNU761 cell system. TM4SF5 expression in SNU761 cells caused invasive extracellular matrix degradation negatively depending on IL-6/IL-6 receptor (IL-6R) signaling. Thus, it is likely that hepatic cancer cells adopt TM4SF5-dependent FAK activation and metastatic potential by lowering IL-6 expression and avoiding its immunological action through the IL-6-STAT3 pathway. 相似文献