收费全文 | 62852篇 |
免费 | 17958篇 |
国内免费 | 3468篇 |
2024年 | 73篇 |
2023年 | 426篇 |
2022年 | 1173篇 |
2021年 | 2411篇 |
2020年 | 3365篇 |
2019年 | 5180篇 |
2018年 | 5219篇 |
2017年 | 5115篇 |
2016年 | 5595篇 |
2015年 | 6233篇 |
2014年 | 6367篇 |
2013年 | 6958篇 |
2012年 | 5233篇 |
2011年 | 4668篇 |
2010年 | 4935篇 |
2009年 | 3589篇 |
2008年 | 2748篇 |
2007年 | 2097篇 |
2006年 | 1803篇 |
2005年 | 1645篇 |
2004年 | 1353篇 |
2003年 | 1291篇 |
2002年 | 1152篇 |
2001年 | 868篇 |
2000年 | 771篇 |
1999年 | 692篇 |
1998年 | 378篇 |
1997年 | 307篇 |
1996年 | 316篇 |
1995年 | 305篇 |
1994年 | 266篇 |
1993年 | 196篇 |
1992年 | 262篇 |
1991年 | 186篇 |
1990年 | 180篇 |
1989年 | 158篇 |
1988年 | 115篇 |
1987年 | 93篇 |
1986年 | 75篇 |
1985年 | 92篇 |
1984年 | 51篇 |
1983年 | 48篇 |
1982年 | 44篇 |
1981年 | 27篇 |
1980年 | 18篇 |
1979年 | 20篇 |
1977年 | 16篇 |
1974年 | 16篇 |
1972年 | 16篇 |
1971年 | 14篇 |
Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a long non-coding RNA (lncRNA), has been reported to link with the progression of some cancers. However, its biological functions and underlying molecular mechanisms in pancreatic cancer are largely unknown. The aim of this study was to investigate the role of lncRNA OIP5-AS1 in pancreatic cancer. Quantitative real-time PCR analysis revealed that OIP5-AS1 is highly expressed in pancreatic cancer tissues versus adjacent non-tumor tissues. In vitro functional assays showed that downregulation of OIP5-AS1 or overexpression of miR-342-3p inhibited the proliferation, decreased Ki67 expression, and induced cell cycle arrest in pancreatic cancer cells. The expression of cyclinD1, CDK4, and CDK6 was decreased by knockdown of OIP5-AS1. Moreover, we found that OIP5-AS1 acted as a miR-342-3p sponge to suppress its expression and function. Dual-luciferase assay confirmed the interaction of OIP5-AS1 and miR-342-3p and verified anterior gradient 2 (AGR2) as a direct target of miR-342-3p. Results showed that depletion of miR-342-3p abolished the inhibitory effects of OIP5-AS1 knockdown on pancreatic cancer cell growth. The expression of Ki67, AGR2, cyclinD1, CDK4, CDK6, p-AKT, and p-ERK1/2 was reversed by silencing of miR-342-3p in pancreatic cancer cells with OIP5-AS1 knockdown. Further, knockdown of OIP5-AS1 suppressed tumor growth in a xenograft mouse model of pancreatic cancer. OIP5-AS1 induced pancreatic cancer progression via activation of AKT and ERK signaling pathways. Therefore, we demonstrate that OIP5-AS1 functions as oncogene in pancreatic cancer and its downregulation inhibits pancreatic cancer growth by sponging miR-342-3p via targeting AGR2 through inhibiting AKT/ERK signaling pathway.
相似文献Streptococcus pneumoniae is a Gram-positive pathogen with high morbidity and mortality globally but some of its pathogenesis remains unknown. Previous research has provided evidence that aminopeptidase N (PepN) is most likely a virulence factor of S. pneumoniae. However, its role in S. pneumoniae virulence and its interaction with the host remains to be confirmed. We generated a pepN gene deficient mutant strain and found that its virulence for mice was significantly attenuated as were in vitro adhesion and invasion of host cells. The PepN protein could induce a strong innate immune response in vivo and in vitro and induced secretion of IL-6 and TNF-α by primary peritoneal macrophages via the rapid phosphorylation of MAPK and PI3K/AKT signaling pathways and this was confirmed using specific pathway inhibitors. In conclusion, PepN is a novel virulence factor that is essential for the virulence of S. pneumoniae and induces host innate immunity via MAPK and PI3K/AKT signaling.
相似文献