全文获取类型
收费全文 | 1003篇 |
免费 | 135篇 |
国内免费 | 111篇 |
出版年
2024年 | 1篇 |
2023年 | 11篇 |
2022年 | 13篇 |
2021年 | 41篇 |
2020年 | 35篇 |
2019年 | 40篇 |
2018年 | 39篇 |
2017年 | 43篇 |
2016年 | 48篇 |
2015年 | 64篇 |
2014年 | 68篇 |
2013年 | 62篇 |
2012年 | 101篇 |
2011年 | 84篇 |
2010年 | 49篇 |
2009年 | 50篇 |
2008年 | 47篇 |
2007年 | 28篇 |
2006年 | 45篇 |
2005年 | 34篇 |
2004年 | 39篇 |
2003年 | 53篇 |
2002年 | 41篇 |
2001年 | 35篇 |
2000年 | 29篇 |
1999年 | 26篇 |
1998年 | 12篇 |
1997年 | 13篇 |
1996年 | 11篇 |
1995年 | 14篇 |
1994年 | 11篇 |
1993年 | 12篇 |
1992年 | 16篇 |
1991年 | 7篇 |
1990年 | 7篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
排序方式: 共有1249条查询结果,搜索用时 234 毫秒
111.
Huang Y Corbley MJ Tang Z Yang L Peng Y Zhang ZY Tong TJ 《Journal of cellular physiology》2004,201(3):483-491
It has been suggested that genes which exercise checkpoint control during cell cycle traverse are equally important to the process of apoptotic cell death. In this study, we show that the key cell cycle regulatory gene p21(WAF1) is also involved in the execution of apoptosis. p21(WAF1) expression was down-regulated during NaBu-induced apoptosis of senescent normal diploid human 2BS fibroblasts. Conversely, when p21(WAF1) expression was actively suppressed in 2BS cells by a stably transfected antisense p21(WAF1) construct, apoptosis was accelerated and senescence was delayed, as shown by several markers of cell aging. Down-regulation of p21(WAF1) by antisense caused an increase in the phosphorylation and inactivation of pRb. Phosphorylation of pRb was further enhanced upon induction of apoptosis by NaBu. Our results suggest that p21(WAF1), acting through the phosphorylation of pRb, regulates whether 2BS cells cease to proliferate and become senescent but resistant to apoptosis, or whether they accelerate proliferation while becoming more susceptible to apoptotic stimuli. 相似文献
112.
小鼠子宫颈部位输卵管蛋白表达的初步研究 总被引:2,自引:0,他引:2
用RT-PCR及免疫印迹法检测证实小鼠子宫颈粘膜上皮细胞具表达输卵管蛋白的能力,宫颈部所获得的输卵管蛋白转录产物, 310到 714的405bp的cDNA片段经序列测定及blast比较表明与输卵管部位表达的输卵管蛋白完全一致(100%)。小鼠子宫颈输卵管蛋白在动情周期的表达波动情况与输卵管粘膜上皮的类似,其表达于小鼠动情期明显增加。Westernblot显示小鼠子宫颈提取物中存在两种不同分子量(60KD,30KD)的输卵管蛋白。原位杂交结果则提示子宫颈粘膜上皮细胞含丰富的输卵管蛋白mRNA信号。通过"原体中风"实验未发现输卵管蛋白在体外对精子活动有影响,其功能尚须进一步分析。 相似文献
113.
目的:为进一步研究抗癫痫肽(And—epilepsy peptide,AEP)的抗痫机制及筛选其相关作用蛋白,进行GST/AEP融合蛋白原核表达载体的构建及融合蛋白的表达。方法:通过PCR基因扩增对AEP基因进行扩增,并将其克隆于谷胱甘肽-S-转移酶(GST)融合蛋白表达质粒pGEX-4T-1中,经酶切、序列鉴定分析后,用该重组质粒转化大肠杆菌B121(DE3),经IPTG诱导获得表达,并采用Western Blot进行检测。结果:成功构建了AEP原核表达载体,并在大肠杆菌B121中获得表达。结论:成功构建了GST/AEP原核表达载体,并表达了GST/AEP融合蛋白。 相似文献
114.
Two types of sulfated octyl tetra- to octaoligofucosides with different sulfation patterns were synthesized employing a combination of stepwise elongation and convergent strategies in which trichloroacetimidates and thioglycosides were selected as the glycosyl donors. 相似文献
115.
RACK1 recruits STAT3 specifically to insulin and insulin-like growth factor 1 receptors for activation, which is important for regulating anchorage-independent growth 下载免费PDF全文
Zhang W Zong CS Hermanto U Lopez-Bergami P Ronai Z Wang LH 《Molecular and cellular biology》2006,26(2):413-424
Current understanding of the activation of STATs is through binding between the SH2 domain of STATs and phosphotyrosine of tyrosine kinases. Here we demonstrate a novel role of RACK1 as an adaptor for insulin and insulin-like growth factor 1 receptor (IGF-1R)-mediated STAT3 activation specifically. Intracellular association of RACK1 via its N-terminal WD domains 1 to 4 (WD1-4) with insulin receptor (IR)/IGF-1R is augmented upon respective ligand stimulation, whereas association with STAT3 is constitutive. Purified RACK1 or RACK1 WD1-4 associates directly with purified IR, IGF-1R, and STAT3 in vitro. Insulin induces multiprotein complex formation of RACK1, IR, and STAT3. Overexpression or downregulation of RACK1 greatly enhances or decreases, respectively, IR/IGF-1R-mediated activation of STAT3 and its target gene expression. Site-specific mutants of IR and IGF-1R impaired in RACK1 binding are ineffective in mediating recruitment and activation of STAT3 as well as in insulin- or IGF-1-induced protection of cells from anoikis. RACK1-mediated STAT3 activation is important for insulin and IGF-1-induced anchorage-independent growth in certain ovarian cancer cells. We conclude that RACK1 mediates recruitment of STAT3 to IR and IGF-1R specifically for activation, suggesting a general paradigm for the need of an adaptor in mediating activation of STATs by receptor protein tyrosine kinases. 相似文献
116.
Li Z Zong H Kong X Zhang S Wang H Sun Q Gu J 《Molecular and cellular biochemistry》2006,291(1-2):69-76
Our previous studies have shown that overexpression of β1,4-galactosyltransferase1 (β1,4GT1) leads to increased apoptosis induced by cycloheximide (CHX) in SMMC-7721 human hepatocarcinoma cells. However, the role of β1,4GT1 in apoptosis remains unclear. Here we demonstrated that cell surface β1,4GT1 inhibited the autophosphorylation of epidermal growth factor receptor (EGFR) especially at Try 1068. The phosphorylation of protein kinase B (PKB/Akt) and extracellular signal-regulated protein kinase1/2 (ERK1/2), which are downstream molecules of EGFR, were also reduced in cell surface β1,4GT1-overexpressing cells. Furthermore, the translocations of Bad and Bax that are regulated by PKB/Akt and ERK1/2 were also increased in these cells. As a result, the release of cytochrome c from mitochondria to cytosol was increased and caspase-3 was activated. In contrast, RNAi-mediated knockdown of β1,4GT1 increased the autophosphorylation of EGFR. These results demonstrated that cell surface β1,4GT1 may negatively regulate cell survival possibly through inhibiting and modulating EGFR signaling pathway. 相似文献
117.
118.
119.
An integrated platform for a very sensitive detection of cocaine based on a refractometric biosensor is demonstrated. The system uses a waveguide grating biosensor functionalized with a cocaine multivalent antigen-carrier protein conjugate. The immunoassay scheme consists of the competitive binding of cocaine-specific antibodies to the immobilized conjugates. A 1000-fold enhancement of the sensor's sensitivity is achieved when using gold conjugated monoclonal antibodies instead of free antibodies. Together with the optimization of the assay conditions, the setup is designed for a quick identification of narcotics using automated sampling. The results show that the presence of cocaine in a liquid sample could be identified down to a concentration of 0.7 nM within one minute. This value can be reduced even further when longer binding time is allowed (0.2 nM after 15 min). Application of the system to detection of narcotics at airport security control points is discussed. 相似文献
120.
Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells 总被引:1,自引:0,他引:1