全文获取类型
收费全文 | 1122篇 |
免费 | 76篇 |
国内免费 | 62篇 |
出版年
2024年 | 1篇 |
2023年 | 18篇 |
2022年 | 33篇 |
2021年 | 80篇 |
2020年 | 43篇 |
2019年 | 58篇 |
2018年 | 49篇 |
2017年 | 41篇 |
2016年 | 61篇 |
2015年 | 103篇 |
2014年 | 73篇 |
2013年 | 114篇 |
2012年 | 120篇 |
2011年 | 95篇 |
2010年 | 65篇 |
2009年 | 34篇 |
2008年 | 43篇 |
2007年 | 24篇 |
2006年 | 29篇 |
2005年 | 19篇 |
2004年 | 18篇 |
2003年 | 5篇 |
2002年 | 17篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 15篇 |
1998年 | 7篇 |
1997年 | 11篇 |
1996年 | 8篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1983年 | 1篇 |
排序方式: 共有1260条查询结果,搜索用时 281 毫秒
991.
microRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by targeting mRNAs, inhibiting the expression of the associated proteins. Although a role for aberrant miRNA expression in cancer has been postulated, the pathophysiologic role and relevance of aberrantly expressed miRNAs in tumor biology has not been established. We evaluated the expression pattern of miRNAs in human breast cancer cells by qPCR, finding out an up-regulated miRNA miR-29b and studying its biological effect by migration assay. We defined a target gene PTEN by bioinformatics approach and western blot. In breast cancer cell line MDA-MB-231 cell, which migrate faster than MCF-7, we observed that miR-29b was highly over-expressed. Inhibition of miR-29b in cultured cells increased the expression of the phosphatase and tensin homolog (PTEN) tumor suppressor, promoting apoptosis, decreasing migration, and decreasing invasion. In contrast, enhanced miR-29b expression by transfection with pre-miR-29b decreased the expression of PTEN and impaired apoptosis, increasing tumor cell migration and invasion. Moreover, PTEN was shown to be a direct target of miR-29b and was also shown to contribute to the miR-29b-mediated effects on cell invasion. Modulation of miR-29b altered the role of PTEN involved in cell migration and invasion. Aberrant expression of miR-29b, which modulates PTEN expression, can contribute to migration, invasion, and anti-apoptosis. 相似文献
992.
993.
994.
The prolongation of QT intervals in both mothers and fetuses during the later period of pregnancy implies that higher levels of progesterone may regulate the function of the human ether-a-go-go-related gene (HERG) potassium channel, a key ion channel responsible for controlling the length of QT intervals. Here, we studied the effect of progesterone on the expression, trafficking, and function of HERG channels and the underlying mechanism. Treatment with progesterone for 24 h decreased the abundance of the fully glycosylated form of the HERG channel in rat neonatal cardiac myocytes and HERG-HEK293 cells, a cell line stably expressing HERG channels. Progesterone also concentration-dependently decreased HERG current density, but had no effect on voltage-gated L-type Ca(2+) and K(+) channels. Immunofluorescence microscopy and Western blot analysis show that progesterone preferentially decreased HERG channel protein abundance in the plasma membrane, induced protein accumulation in the dilated endoplasmic reticulum (ER), and increased the protein expression of C/EBP homologous protein, a hallmark of ER stress. Application of 2-hydroxypropyl-β-cyclodextrin (a sterol-binding agent) or overexpression of Rab9 rescued the progesterone-induced HERG trafficking defect and ER stress. Disruption of intracellular cholesterol homeostasis with simvastatin, imipramine, or exogenous application of cholesterol mimicked the effect of progesterone on HERG channel trafficking. Progesterone may impair HERG channel folding in the ER and/or block its trafficking to the Golgi complex by disrupting intracellular cholesterol homeostasis. Our findings may reveal a novel molecular mechanism to explain the QT prolongation and high risk of developing arrhythmias during late pregnancy. 相似文献
995.
996.
Tewary SK Oda T Kendall A Bian W Stubbs G Wong SM Swaminathan K 《Journal of molecular biology》2011,406(3):516-526
Hibiscus latent Singapore virus (HLSV) is a rigid rod-shaped plant virus and a new member of the Tobamovirus family. Unlike all other Tobamoviruses, the HLSV genome contains a unique poly(A) tract in its 3′ untranslated region. The virion is composed of a monomeric coat protein (CP) unit of 18 kDa, arranged as a right-handed helix around the virus axis. We have determined the structure of HLSV at 3.5 Å by X-ray fiber diffraction and refined it to an R-factor of 0.096. While the overall structure of the HLSV CP resembles that of other Tobamoviruses, there are a few unique differences. There is a kink in the LR helix due to the presence of His122. Also, the adjacent Lys123 may further destabilize the helix by positive charge repulsion, making the kink more pronounced. The His122-Asp88 salt bridge provides significant stability to the loop adjacent to the RR helix. Carboxyl-carboxylate interactions that drive viral disassembly are also different in HLSV. The nucleotide recognition mechanisms for virus assembly between HLSV and ribgrass mosaic virus are similar, but different between tobacco mosaic virus and cucumber green mottle mosaic virus. 相似文献
997.
Xu F Chen YG Xue L Li RJ Zhang H Bian Y Zhang C Lv RJ Feng JB Zhang Y 《Journal of cellular and molecular medicine》2011,15(9):1955-1962
This study aimed to investigate the association of the aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism, which exists in 30-50% of East Asians, and risk of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese, including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2 mutant genotypes showed significantly higher ACS than did controls (46.7% versus 31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval [CI]: 1.31-2.92, P = 0.001), but the association was weaker on adjusting for alcohol consumption (OR 1.82, 95% CI: 1.23-2.70, P = 0.003). Similar results were found in a subgroup analysis of patients with primary ST-segment elevation myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P = 0.002) and in controls (P = 0.009) and number of circulating endothelial progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and EPCs number as independent variables in regression analysis reduced the importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2 polymorphism was not associated with number of coronary arteries with significant stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is explained in part by alcohol consumption, inflammation and number of circulating EPCs. 相似文献
998.
999.
1000.
脓毒症是内外科危重病患者常见的并发症,近年来全球发病率明显增高,且以每年1.5%-8%的速度增加,成为危重病患者的主要死亡原因之一,随着其发病机制的进一步研究,胃肠道的屏障功能越来越受到重视,传统的治疗措施未能明显改善病死率,且大量以抗炎症介质的实验以失败告终.而近年来中医药在危重症患者中的作用越来越受到重视,中西医结合治疗的病死率远远低于目前国际病死率,本文对中医药治疗脓毒症患者胃肠功能进展及现状做如下综述,并简单分析了目前存在的问题和解决办法. 相似文献