全文获取类型
收费全文 | 473篇 |
免费 | 26篇 |
国内免费 | 31篇 |
专业分类
530篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2022年 | 12篇 |
2021年 | 18篇 |
2020年 | 14篇 |
2019年 | 16篇 |
2018年 | 14篇 |
2017年 | 8篇 |
2016年 | 8篇 |
2015年 | 24篇 |
2014年 | 34篇 |
2013年 | 30篇 |
2012年 | 36篇 |
2011年 | 39篇 |
2010年 | 9篇 |
2009年 | 24篇 |
2008年 | 16篇 |
2007年 | 21篇 |
2006年 | 9篇 |
2005年 | 21篇 |
2004年 | 20篇 |
2003年 | 24篇 |
2002年 | 20篇 |
2001年 | 17篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 7篇 |
1997年 | 12篇 |
1996年 | 2篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有530条查询结果,搜索用时 15 毫秒
81.
A proteomics approach to identifying novel protein targets involved in erinacine A–mediated inhibition of colorectal cancer cells’ aggressiveness
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ko‐Chao Lee Hsing‐Chun Kuo Chien‐Heng Shen Chien‐Chang Lu Wen‐Shih Huang Meng‐Chiao Hsieh Cheng‐Yi Huang Yi‐Hung Kuo Yung‐Yu Hsieh Chih‐Chuan Teng Li‐Ya Lee Shui‐Yi Tung 《Journal of cellular and molecular medicine》2017,21(3):588-599
Erinacine A, a major active component of a diterpenoid derivative isolated from Hericium erinaceus mycelium, has been demonstrated to exert anticancer effects. Herein, we present an investigation of the molecular mechanism of erinacine A induction associated with cancer cells’ aggressive status and death. A proteomic approach was used to purify and identify the differentially expressed proteins following erinacine A treatment and the mechanism of its action in apoptotic and the targets of erinacine A. Our results demonstrate that erinacine A treatment of HCT‐116 and DLD‐1 cells increased cell cytotoxicity and reactive oxygen species (ROS) production as well as decreased cell proliferation and invasiveness. Ten differentially displayed proteins were determined and validated in vitro and in vivo between the erinacine A‐treated and untreated groups. In addition, erinacine A time‐dependent induction of cell death and inhibitory invasiveness was associated with sustained phosphorylation of the PI3K/mTOR/p70S6K and ROCK1/LIMK2/Cofilin pathways. Furthermore, we demonstrated that erinacine A–induced HCT‐116 and DLD‐1 cells viability and anti‐invasion properties by up‐regulating the activation of PI3K/mTOR/p70S6K and production of ROS. Experiments involving specific inhibitors demonstrated that the differential expression of cofilin‐1 (COFL1) and profilin‐1 (PROF1) during erinacine A treatment could be involved in the mechanisms of HCT‐116 and DLD‐1 cells death and decreased aggressiveness, which occurred via ROCK1/LIMK2/Cofilin expression, with activation of the PI3K/mTOR/p70S6K signalling pathway. These findings elucidate the mechanism of erinacine A inhibiting the aggressive status of cells by activating PI3K/mTOR/p70S6K downstream signalling and the novel protein targets COF1 and PROF1; this could be a good molecular strategy to limit the aggressiveness of CRC cells. 相似文献
82.
83.
从酵母表达时间序列估计基因调控网络 总被引:10,自引:0,他引:10
基因调控网络是生命功能在基因表达层面上的展现。用组合线性调控模型、调控元件识别和基因聚类等方法 ,从基因组表达谱解读酵母在细胞周期与环境胁迫中的基因调控网络。结果表明 ,细胞在不同环境条件下会调整基因调控网络。在适应的环境下 ,起主要作用的是细胞生长和增殖有关的基因调控网络 ;而在响应环境胁迫时 ,细胞会再规划调控网络 ,抑制细胞生长和增殖相关的基因 ,诱导跟适应性糖类代谢与结构修复相关的基因 ,还可能启动减数分裂产生孢子。分别从细胞周期和环境胁迫响应相关基因中 ,搜索到转录因子Mcm1结合位点TT CC T GGAAA ,和Dal82在尿囊素代谢途径相关基因上的结合位点TGAAAAWTTT。从而 ,从酵母表达时间序列估计基因调控网络是可行的 ,与至今已知的实验观察相当吻合 相似文献
84.
85.
Xian-Xing Xu Xue Shui Zhi-Hang Chen Cheng-Qi Shan Yu-Nan Hou Yuan-Guo Cheng 《Molecular biotechnology》2009,43(2):130-137
A replication-deficient recombinant adenovirus (Ad5-LFA-3/IgG1) that encodes secreted LFA-3/IgG1 was constructed for gene therapy treatment of psoriasis. The purpose of this study was to develop a real-time PCR method
for pharmacokinetic and biodistribution studies of Ad5-LFA-3/IgG1 within the circulation and organs. This method showed good specificity, sensitivity and reproducibility over a wide dynamic
range of concentrations. Quantitative measurement of recombinant adenoviral DNA suggested that the level of Ad5-LFA-3/IgG1 DNA in circulating blood peaked within 10 min following intravenous injection in rhesus macaques. Following this peak, the
adenoviral DNA level dropped significantly to a very low level. Real-time PCR revealed that Ad5-LFA-3/IgG1 DNA was enriched in the spleen, lung and liver after injection of the adenovirus into rats through the tail vein. The adenoviral
DNA was barely detected in other tissues. These data provide important information for clinical trials of Ad5-LFA-3/IgG1 and confirm the utility of the real-time PCR assay for monitoring gene therapy trials. 相似文献
86.
Prediction and analysis of molecular structure and biochemical function are of theoretical guiding significance for gene discovery
and application, and considered as one of the central problem of computational biology. Here, some characteristic features
of chalcone synthase (CHS) family from Scutellaria baicalensis were described via bioinformatic analysis, and showed as following: the nucleic acid sequences and amino acid sequences of
three chs member genes shared high similarity in the molecular structures and physicochemical properties; SbCHS proteins were localized
to the cytosol, and possessed a good hydrophobic nature, with lacking any transmembrane topological structure. The phylogram
analysis suggested that they were a group genes with significant functional association and genetic conservation. The secondary
structures of the SbCHSs were mainly composed of α-helixes and random coils, and the tertiary structures contained malonyl
CoA linkers, besides, each of CHS-A and CHS-B with N-glycosylation motif included. Taken together, these results demonstrate
that CHS family from S. baicalensis has the typical molecular structure and function of chalcone synthase, compared with the experimental data for Medicago sativa CHS protein. 相似文献
87.
88.
Fei W Li H Shui G Kapterian TS Bielby C Du X Brown AJ Li P Wenk MR Liu P Yang H 《Journal of lipid research》2011,52(12):2136-2147
The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin has been implicated in adipocyte differentiation, lipid droplet (LD) formation, and motor neuron development. However, the molecular function of seipin and its disease-causing mutants remains to be elucidated. Here, we characterize seipin and its mis-sense mutants: N88S/S90L (both linked to motoneuron disorders) and A212P (linked to lipodystrophy) in cultured mammalian cells. Knocking down seipin significantly increases oleate incorporation into triacylglycerol (TAG) and the steady state level of TAG, and induces the proliferation and clustering of small LDs. By contrast, overexpression of seipin reduces TAG synthesis, leading to decreased formation of LDs. Expression of the A212P mutant, however, had little effect on LD biogenesis. Surprisingly, expression of N88S or S90L causes the formation of many small LDs reminiscent of seipin deficient cells. This dominant-negative effect may be due to the N88S/S90L-induced formation of inclusions where wild-type seipin can be trapped. Importantly, coexpression of wild-type seipin and the N88S or S90L mutant can significantly reduce the formation of inclusions. Finally, we demonstrate that seipin can interact with itself and its mutant forms. Our results provide important insights into the biochemical characteristics of seipin and its mis-sense mutants, and suggest that seipin may function to inhibit lipogenesis. 相似文献
89.
90.