收费全文 | 32125篇 |
免费 | 3102篇 |
国内免费 | 1785篇 |
2023年 | 298篇 |
2022年 | 616篇 |
2021年 | 1280篇 |
2020年 | 886篇 |
2019年 | 1124篇 |
2018年 | 1108篇 |
2017年 | 800篇 |
2016年 | 1183篇 |
2015年 | 1680篇 |
2014年 | 1921篇 |
2013年 | 2031篇 |
2012年 | 2475篇 |
2011年 | 2222篇 |
2010年 | 1349篇 |
2009年 | 1276篇 |
2008年 | 1541篇 |
2007年 | 1337篇 |
2006年 | 1191篇 |
2005年 | 984篇 |
2004年 | 832篇 |
2003年 | 737篇 |
2002年 | 639篇 |
2001年 | 1419篇 |
2000年 | 1264篇 |
1999年 | 1007篇 |
1998年 | 416篇 |
1997年 | 462篇 |
1996年 | 359篇 |
1995年 | 328篇 |
1994年 | 310篇 |
1993年 | 232篇 |
1992年 | 535篇 |
1991年 | 460篇 |
1990年 | 420篇 |
1989年 | 312篇 |
1988年 | 286篇 |
1987年 | 222篇 |
1986年 | 207篇 |
1985年 | 171篇 |
1984年 | 105篇 |
1983年 | 110篇 |
1982年 | 49篇 |
1981年 | 44篇 |
1979年 | 50篇 |
1978年 | 39篇 |
1976年 | 45篇 |
1975年 | 41篇 |
1973年 | 47篇 |
1972年 | 53篇 |
1971年 | 51篇 |
Kawasaki disease (KD) causes cardiovascular system injury in children. However, the pathogenic mechanisms of KD have not been well defined. Recently, strong correlation between aberrant microRNAs and KD nosogenesis has been revealed. A role of microRNA-197-3p (miR-197-3p) in the pathogenesis of KD is identified in the present study. Cell proliferation assay showed human coronary artery endothelial cells (HCAECs) were suppressed by serum from KD patients, which was correlated with high levels of miR-197-3p in both KD serum and HCAECs cultured with KD serum. The inhibition of HCAECs by miR-197-3p was confirmed by cells expressing miR-197-3p mimic and miR-197-3p inhibitor. Comparative proteomics analysis and Ingenuity Pathway Analysis (IPA) revealed TIMP3 as a potential target of miR-197-3p, which was demonstrated by western blot and dual-luciferase reporter assays. Subsequently, by detecting the endothelium damage markers THBS1, VWF, and HSPG2, the role of miR-197-3p/TIMP3 in KD-induced damage to HCAECs was confirmed, which was further validated by a KD mouse model in vivo. The expressions of miR-197-3p and its target, TIMP3, are dramatically variational in KD serum and HCAECs cultured with KD serum. Increased miR-197-3p induces HCAECs abnormal by restraining TIMP3 expression directly. Hence, dysregulation of miR-197-3p/TIMP3 expression in HCAECs may be an important mechanism in cardiovascular endothelium injury in KD patients, which offers a feasible therapeutic target for KD treatment.
相似文献Intracerebral hemorrhage (ICH) causes long term neurological abnormality or death. Oxidative stress is closely involved in ICH mediated brain damage. Steroid receptor cofactor 3 (SRC-3), a p160 family member, is widely expressed in the brain and regulates transactivation of Nrf2, a key component of antioxidant response. Our study aims to test if SRC-3 is implicated in ICH mediated brain injury. We first examined levels of SRC-3 and oxidative stress in the brain of mice following ICH and analyzed their correlation. Then ICH was induced in wild type (WT) and SRC-3 knock out mice and how SRC-3 deletion affected ICH induced brain damage, oxidative stress and behavioral outcome was assessed. We found that SRC-3 mRNA and protein expression levels were reduced gradually after ICH induction in WT mice along with an increase in oxidative stress levels. Correlation analysis revealed that SRC-3 mRNA levels negatively correlated with oxidative stress. Deletion of SRC-3 further increased ICH induced brain edema, neurological deficit score and oxidative stress and exacerbated ICH induced behavioral abnormality including motor dysfunction and cognitive impairment. Our findings suggest that SRC-3 is involved in ICH induced brain injury, probably through modulation of oxidative stress.
相似文献