收费全文 | 46774篇 |
免费 | 4162篇 |
国内免费 | 7959篇 |
2024年 | 104篇 |
2023年 | 756篇 |
2022年 | 1007篇 |
2021年 | 2650篇 |
2020年 | 1869篇 |
2019年 | 2258篇 |
2018年 | 2036篇 |
2017年 | 1557篇 |
2016年 | 1975篇 |
2015年 | 2923篇 |
2014年 | 3464篇 |
2013年 | 3714篇 |
2012年 | 4486篇 |
2011年 | 3946篇 |
2010年 | 2776篇 |
2009年 | 2432篇 |
2008年 | 2828篇 |
2007年 | 2543篇 |
2006年 | 2421篇 |
2005年 | 1981篇 |
2004年 | 1578篇 |
2003年 | 1367篇 |
2002年 | 1185篇 |
2001年 | 1074篇 |
2000年 | 962篇 |
1999年 | 864篇 |
1998年 | 464篇 |
1997年 | 450篇 |
1996年 | 382篇 |
1995年 | 369篇 |
1994年 | 362篇 |
1993年 | 296篇 |
1992年 | 344篇 |
1991年 | 263篇 |
1990年 | 232篇 |
1989年 | 200篇 |
1988年 | 152篇 |
1987年 | 116篇 |
1986年 | 111篇 |
1985年 | 104篇 |
1984年 | 73篇 |
1983年 | 69篇 |
1982年 | 55篇 |
1981年 | 24篇 |
1980年 | 15篇 |
1979年 | 14篇 |
1958年 | 4篇 |
1957年 | 7篇 |
1954年 | 4篇 |
1953年 | 4篇 |
FK1706 is a novel non-immunosuppressive immunophilin ligand with neurotrophic activity and exerts its neurotrophic effect through NGF. The present study aimed to elaborate on the neurotrophic activity and the mechanism of action of FK1706 in end-to-side neurorrhaphy rats and SH-SY5Y cells. In the regenerating nerves of neurorrhaphy rats, FK1706 increased the thickness of myelin sheath and the level of nerve regeneration-related proteins. The mechanism of action of FK1706 on neurite regrowth was elucidated in vitro by incubating SH-SY5Y cells in different conditions (Control, NGF, FK1706, NGF?+?FK1706, NGF?+?FK1706?+?geldanamycin). Under the conditions where NGF was used, the phosphorylation level of major proteins (Raf-1 and ERK) in the Ras/Raf/MAPK/ERK signaling pathway related to SH-SY5Y cell proliferation was significantly enhanced following the application of FK1706. The number of viable cells, cell viability and neurite length of SH-SY5Y cells was maximal when NGF and FK1706 were used simultaneously. The binding level of HSP90 and Raf-1 in FK1706 group was the highest. These results indicated that FK1706 could significantly promote nerve regeneration after neurorrhaphy. The putative mechanism of action stated that FK1706 could promote the binding of HSP90 and Raf-1, make Raf-1 continue to be activated, thereby affecting key proteins in the Ras/Raf/MAPK/ERK signaling pathway related to the neurotrophic effects of NGF to promote the proliferation and neurite regrowth of nerve cells.
相似文献We aimed to illustrate the roles and molecular mechanisms of ID2-AS1 in parkinson’s disease (PD). Methods: qRT-PCR detected the expression of ID2-AS1. CCK-8, LDH release assays the effect of ID2-AS1 knockdown on PD cells. Flow cytometry and Western Blot were used to detect the effect of ID2-AS1 inhibition on PD cell apoptosis. ELISA analysis showed that ID2-AS1 inhibition can reduce the inflammation of PD cells. ROS activity assay showed that inhibiting ID2-AS1 attenuated the oxidative stress induced by 1-methy1-4-phenylpyridinium (MPP+). RNA binding protein immunoprecipitation assay showed that ID2-AS1 is mainly located in the cytoplasm. The luciferase reporter assay is used to verify the interaction. In our study, ID2-AS1 was concentration-dependently and time-dependently up-regulated in MPP+?-treated human neuroblastoma cell line SH-SY5Y. ID2-AS1 knockdown enhanced cell proliferation and decreased cell death in PD cells. Knockdown of ID2-AS1 attenuates MPP+?-induced cytotoxicity in SH-SY5Y cells. ID2-AS1 is a sponge of miR-199a-5p. IFNAR1 is a target of miR-199a-5p. Inhibition of miR-199a-5p and overexpression of IFNAR1 alleviate the inhibitory effect of ID2-AS1 knockdown on MPP+?triggered neuronal injury. Inhibition of miR-199a-5p and overexpression of IFNAR1 alleviate the inhibitory effect of ID2-AS1 knockdown on MPP+?-triggered JAK2/STAT1 activation. Overall, down-regulation of ID2-AS1 alleviated the neuronal injury in PD through regulating miR-199a-5p/IFNAR1/JAK2/STAT1 axis.
相似文献