全文获取类型
收费全文 | 551篇 |
免费 | 58篇 |
出版年
2022年 | 4篇 |
2021年 | 10篇 |
2020年 | 6篇 |
2019年 | 7篇 |
2018年 | 5篇 |
2017年 | 4篇 |
2016年 | 11篇 |
2015年 | 20篇 |
2014年 | 27篇 |
2013年 | 21篇 |
2012年 | 32篇 |
2011年 | 27篇 |
2010年 | 18篇 |
2009年 | 26篇 |
2008年 | 27篇 |
2007年 | 29篇 |
2006年 | 22篇 |
2005年 | 21篇 |
2004年 | 28篇 |
2003年 | 29篇 |
2002年 | 17篇 |
2001年 | 22篇 |
2000年 | 26篇 |
1999年 | 21篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1992年 | 8篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 12篇 |
1985年 | 9篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1975年 | 5篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1968年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有609条查询结果,搜索用时 250 毫秒
601.
602.
Lauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophages
Tham Yong Yao Choo Quok Cheong Muhammad Tengku Sifzizul Tengku Chew Choy Hoong 《Molecular biology reports》2020,47(12):9595-9607
Molecular Biology Reports - Mitochondrial dysfunction plays a crucial role in the central pathogenesis of insulin resistance and type 2 diabetes mellitus. Macrophages play important roles in the... 相似文献
603.
Lars Boeckmann Yoshimitsu Takahashi Wei-Chun Au Prashant K. Mishra John S. Choy Anthony R. Dawson May Y. Szeto Timothy J. Waybright Christopher Heger Christopher McAndrew Paul K. Goldsmith Timothy D. Veenstra Richard E. Baker Munira A. Basrai 《Molecular biology of the cell》2013,24(12):2034-2044
The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We identify posttranslational modifications of Saccharomyces cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants shows growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody, we show that the association of phosphorylated Cse4 with centromeres increases in response to defective microtubule attachment or reduced cohesion. We determine that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 are reduced at centromeres in ipl1 strains in vivo, and in vitro assays show phosphorylation of Cse4 by Ipl1. Consistent with these results, we observe that a phosphomimetic cse4-4SD mutant suppresses the temperature-sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80, which are defective for chromosome biorientation. Furthermore, cell biology approaches using a green fluorescent protein–labeled chromosome show that cse4-4SD suppresses chromosome segregation defects in dam1 spc34 strains. On the basis of these results, we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our results provide a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation. 相似文献
604.
605.
606.
Many researches have shown that anionic clays can be used as delivery carriers for drug or gene molecules due to their efficient cellular uptake in vitro, and enhanced permeability and retention effect in vivo. It is, therefore, highly required to establish a guideline on their potential toxicity for practical applications. The toxicity of anionic clay, layered metal hydroxide nanoparticle, was evaluated in two human lung epithelial cells, carcinoma A549 cells and normal L-132 cells, and compared with that in other human cancer cell lines such as cervical adenocarcinoma cells (HeLa) and osteosarcoma cells (HOS). The present nanoparticles showed little cytotoxic effects on the proliferation and viability of four cell lines tested at the concentrations used (<250 μg/ml) within 48 h. However, exposing cancer cells to high concentrations (250-500 μg/ml) for 72 h resulted in an inflammatory response with oxidative stress and membrane damage, which varied with the cell type (A549 > HOS > HeLa). On the other hand, the toxicity mechanism seems to be different from that of other inorganic nanoparticles frequently studied for biological and medicinal applications such as iron oxide, silica, and single walled carbon nanotubes. Iron oxide caused cell death associated with membrane damage, while single walled carbon nanotube induced oxidative stress followed by apoptosis. Silica triggered an inflammation response without causing considerable cell death for both cancer cells and normal cells, whereas layered metal hydroxide nanoparticle did not show any cytotoxic effects on normal L-132 cells in terms of inflammation response, oxidative stress, and membrane damage at the concentration of less than 250 μg/ml. It is , therefore, highly expected that the present nanoparticle can be used as a efficient vehicle for drug delivery and cancer cell targeting as well. 相似文献
607.
608.
Regulation of proliferation of embryonic heart mesenchyme: role of transforming growth factor-beta 1 and the interstitial matrix 总被引:1,自引:0,他引:1
Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor-beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage. 相似文献
609.
G A McClarty A K Chan B K Choy J A Wright 《The Journal of biological chemistry》1990,265(13):7539-7547
In the present study, we show that hydroxyurea-inactivated ribonucleotide reductase protein M2 has a destabilized iron center, which readily releases iron. In addition, evidence is presented which indicates that single or multistep selection for hydroxyurea resistance, in a variety of mammalian cell lines, leads to alterations in the expression of the gene for the iron storage protein, ferritin. In all hydroxyurea-resistant cell lines examined, including human, hamster, rat, and mouse, there was an elevation in ferritin heavy (H)- and/or light (L)-mRNA levels, but no change in the corresponding gene copy number. A detailed analysis of ferritin expression in a hydroxyurea-resistant mouse L cell line showed that when compared to its wild type counterpart, there was an increase in H subunit concentration but no significant change in L subunit levels. The increased H/L subunit ratio was not brought about by specific changes in the rates of ferritin subunit biosynthesis, but rather resulted from changes in the post-translational stability of H subunits relative to L subunits in the resistant cell line compared to its parental wild type. Also, we show that treatment of cells with hydroxyurea results in an increased rate of ferritin biosynthesis in the absence of changes in H- or L-mRNA levels. These results indicate that the development of even low level hydroxyurea resistance in mammalian cells may require alterations in ferritin gene expression, and they show an interesting relationship between the expressions of two highly regulated activities, ribonucleotide reductase and ferritin. 相似文献