全文获取类型
收费全文 | 666篇 |
免费 | 80篇 |
国内免费 | 16篇 |
出版年
2024年 | 1篇 |
2023年 | 32篇 |
2022年 | 35篇 |
2021年 | 70篇 |
2020年 | 31篇 |
2019年 | 45篇 |
2018年 | 34篇 |
2017年 | 46篇 |
2016年 | 32篇 |
2015年 | 31篇 |
2014年 | 34篇 |
2013年 | 53篇 |
2012年 | 33篇 |
2011年 | 32篇 |
2010年 | 26篇 |
2009年 | 28篇 |
2008年 | 22篇 |
2007年 | 29篇 |
2006年 | 21篇 |
2005年 | 28篇 |
2004年 | 18篇 |
2003年 | 20篇 |
2002年 | 16篇 |
2001年 | 20篇 |
2000年 | 5篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有762条查询结果,搜索用时 15 毫秒
1.
Inflammatory responses mediated by activated microglia play a pivotal role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders. Studies on identification of specific targets to control microglia activation and resultant neurotoxic activity are imperative. Increasing evidence indicate that voltage-gated K+ (Kv) channels are involved in the regulation of microglia functionality. In this study, we investigated Kv1.3 channels in the regulation of neurotoxic activity mediated by HIV-1 glycoprotein 120 (gp120)-stimulated rat microglia. Our results showed treatment of microglia with gp120 increased the expression levels of Kv1.3 mRNA and protein. In parallel, whole-cell patch-clamp studies revealed that gp120 enhanced microglia Kv1.3 current, which was blocked by margatoxin, a Kv1.3 blocker. The association of gp120 enhancement of Kv1.3 current with microglia neurotoxicity was demonstrated by experimental results that blocking microglia Kv1.3 attenuated gp120-associated microglia production of neurotoxins and neurotoxicity. Knockdown of Kv1.3 gene by transfection of microglia with Kv1.3-siRNA abrogated gp120-associated microglia neurotoxic activity. Further investigation unraveled an involvement of p38 MAPK in gp120 enhancement of microglia Kv1.3 expression and resultant neurotoxic activity. These results suggest not only a role Kv1.3 may have in gp120-associated microglia neurotoxic activity, but also a potential target for the development of therapeutic strategies. 相似文献
2.
Aurélie Brécier Vina W. Li Chloé S. Smith Katherine Halievski Nader Ghasemlou 《Biological reviews of the Cambridge Philosophical Society》2023,98(2):520-539
Glial cells are the most abundant cells in the central nervous system and play crucial roles in neural development, homeostasis, immunity, and conductivity. Over the past few decades, glial cell activity in mammals has been linked to circadian rhythms, the 24-h chronobiological clocks that regulate many physiological processes. Indeed, glial cells rhythmically express clock genes that cell-autonomously regulate glial function. In addition, recent findings in rodents have revealed that disruption of the glial molecular clock could impact the entire organism. In this review, we discuss the impact of circadian rhythms on the function of the three major glial cell types – astrocytes, microglia, and oligodendrocytes – across different locations within the central nervous system. We also review recent evidence uncovering the impact of glial cells on the body's circadian rhythm. Together, this sheds new light on the involvement of glial clock machinery in various diseases. 相似文献
3.
4.
5.
6.
《Cell》2022,185(22):4153-4169.e19
7.
Nader Morshed William T Ralvenius Alexi Nott L Ashley Watson Felicia H Rodriguez Leyla A Akay Brian A Joughin PingChieh Pao Jay Penney Lauren LaRocque Diego Mastroeni LiHuei Tsai Forest M White 《Molecular systems biology》2020,16(12)
Alzheimer’s disease (AD) is characterized by the appearance of amyloid‐β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK‐p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec‐F which was upregulated on a subset of reactive microglia. The human paralog Siglec‐8 was also upregulated on microglia in AD. Siglec‐F and Siglec‐8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV‐2 cell line and human stem cell‐derived microglia models. Siglec‐F overexpression activates an endocytic and pyroptotic inflammatory response in BV‐2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine‐based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV‐2 cells. Collectively, our results point to an important role for mouse Siglec‐F and human Siglec‐8 in regulating microglial activation during neurodegeneration. 相似文献
8.
9.