全文获取类型
收费全文 | 33832篇 |
免费 | 3050篇 |
国内免费 | 4674篇 |
出版年
2024年 | 105篇 |
2023年 | 481篇 |
2022年 | 1041篇 |
2021年 | 1760篇 |
2020年 | 1358篇 |
2019年 | 1670篇 |
2018年 | 1505篇 |
2017年 | 1089篇 |
2016年 | 1577篇 |
2015年 | 2233篇 |
2014年 | 2691篇 |
2013年 | 2800篇 |
2012年 | 3303篇 |
2011年 | 2959篇 |
2010年 | 2008篇 |
2009年 | 1767篇 |
2008年 | 2037篇 |
2007年 | 1799篇 |
2006年 | 1574篇 |
2005年 | 1397篇 |
2004年 | 1288篇 |
2003年 | 1128篇 |
2002年 | 932篇 |
2001年 | 512篇 |
2000年 | 420篇 |
1999年 | 383篇 |
1998年 | 308篇 |
1997年 | 243篇 |
1996年 | 187篇 |
1995年 | 174篇 |
1994年 | 144篇 |
1993年 | 98篇 |
1992年 | 105篇 |
1991年 | 90篇 |
1990年 | 73篇 |
1989年 | 59篇 |
1988年 | 42篇 |
1987年 | 29篇 |
1986年 | 23篇 |
1985年 | 27篇 |
1984年 | 17篇 |
1983年 | 17篇 |
1982年 | 18篇 |
1981年 | 14篇 |
1980年 | 8篇 |
1979年 | 9篇 |
1976年 | 6篇 |
1975年 | 5篇 |
1972年 | 6篇 |
1970年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
971.
972.
Background
Mediating DNA damage-induced apoptosis is an important genome-maintenance function of the mismatch repair (MMR) system. Defects in MMR not only cause carcinogenesis, but also render cancer cells highly resistant to chemotherapeutics, including alkylating agents. To understand the mechanisms of MMR-mediated apoptosis and MMR-deficiency-caused drug resistance, we analyze a model alkylating agent (N-methyl-N’-nitro-N-nitrosoguanidine, MNNG)-induced changes in protein phosphorylation and abundance in two cell lines, the MMR-proficient TK6 and its derivative MMR-deficient MT1.Results
Under an experimental condition that MNNG-induced apoptosis was only observed in MutSα-proficient (TK6), but not in MutSα-deficient (MT1) cells, quantitative analysis of the proteomic data revealed differential expression and phosphorylation of numerous individual proteins and clusters of protein kinase substrates, as well differential activation of response pathways/networks in MNNG-treated TK6 and MT1 cells. Many alterations in TK6 cells are in favor of turning on the apoptotic machinery, while many of those in MT1 cells are to promote cell proliferation and anti-apoptosis.Conclusions
Our work provides novel molecular insights into the mechanism of MMR-mediated DNA damage-induced apoptosis.973.
X Zheng J Naiditch M Czurylo C Jie T Lautz S Clark N Jafari Y Qiu F Chu M B Madonna 《Cell death & disease》2013,4(7):e740
Numerous studies have confirmed that cancer stem cells (CSCs) are more resistant to chemotherapy; however, there is a paucity of data exploring the effect of long-term drug treatment on the CSC sub-population. The purpose of this study was to investigate whether long-term doxorubicin treatment could expand the neuroblastoma cells with CSC characteristics and histone acetylation could affect stemness gene expression during the development of drug resistance. Using n-myc amplified SK-N-Be(2)C and non-n-myc amplified SK-N-SH human neuroblastoma cells, our laboratory generated doxorubicin-resistant cell lines in parallel over 1 year; one cell line intermittently treated with the histone deacetylase inhibitor (HDACi) vorinostat and the other without exposure to HDACi. Cells'' sensitivity to chemotherapeutic drugs, the ability to form tumorspheres, and capacity for in vitro invasion were examined. Cell-surface markers and side populations (SPs) were analyzed using flow cytometry. Differentially expressed stemness genes were identified through whole genome analysis and confirmed with real-time PCR. Our results indicated that vorinostat increased the sensitivity of only SK-N-Be(2)C-resistant cells to chemotherapy, made cells lose the ability to form tumorspheres, and reduced in vitro invasion and the SP percentage. CD133 was not enriched in doxorubicin-resistant or vorinostat-treated doxorubicin-resistant cells. Nine stemness-linked genes (ABCB1, ABCC4, LMO2, SOX2, ERCC5, S100A10, IGFBP3, TCF3, and VIM) were downregulated in vorinostat-treated doxorubicin-resistant SK-N-Be(2)C cells relative to doxorubicin-resistant cells. A sub-population of cells with CSC characteristics is enriched during prolonged drug selection of n-myc amplified SK-N-Be(2)C neuroblastoma cells. Vorinostat treatment affects the reversal of drug resistance in SK-N-Be(2)C cells and may be associated with downregulation of stemness gene expression. This work may be valuable for clinicians to design treatment protocols specific for different neuroblastoma patients. 相似文献
974.
975.
Juan Lin Hanjie Li Min Yang Junming Ren Zhe Huang Felicia Han Jian Huang Jianhui Ma Duanwu Zhang Zhirong Zhang Jianfeng Wu Deli Huang Muzhen Qiao Guanghui Jin Qiao Wu Yinghui Huang Jie Du Jiahuai Han 《Cell reports》2013,3(1):200-210
- Download : Download full-size image
976.
Jie Xu Xiaolin Zhou Jilin Wang Zhaoli Li Xuan Kong Jin Qian Ye Hu Jing-Yuan Fang 《Cell reports》2013,3(5):1526-1538
- Download : Download full-size image
977.
- Download : Download full-size image
978.
979.
980.
Titanium alloy is one of the best materials for biomedical applications due to its superior biocompatibility, outstanding corrosion resistance, and low elastic modulus. However, the friction and wear behaviors of titanium alloys were sensitive to the environment including lubrication. In order to clarify the wear mechanism of titanium alloy under different lubrications including deionized water, physiological saline and bovine serum, the friction and wear tests were performed between Ti6Al4V plates and Si3N4 ball on a universal multi-functional tester. The friction and the wear rate of titanium alloy were measured under dry friction and three different lubrication conditions. The worn surfaces were examined by scanning electron microscopy. The results revealed that under the dry friction, the wear resistance of titanium alloy was the worst since the wear mechanism was mainly the combination of abrasive wear and oxidation wear. It was also found that Ti6Al4V alloy had low friction coefficient and wear rate under three lubrication conditions, and its wear mechanism was adhesive wear. 相似文献