全文获取类型
收费全文 | 500篇 |
免费 | 44篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 12篇 |
2015年 | 17篇 |
2014年 | 20篇 |
2013年 | 31篇 |
2012年 | 28篇 |
2011年 | 34篇 |
2010年 | 21篇 |
2009年 | 29篇 |
2008年 | 25篇 |
2007年 | 34篇 |
2006年 | 24篇 |
2005年 | 21篇 |
2004年 | 33篇 |
2003年 | 29篇 |
2002年 | 25篇 |
2001年 | 15篇 |
2000年 | 14篇 |
1999年 | 13篇 |
1998年 | 4篇 |
1997年 | 10篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 12篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有544条查询结果,搜索用时 15 毫秒
101.
102.
103.
范娟 杨瑾 周鑫 董治龙 王李阳 MengMeng Xu 牟玉莲 Miyuki Nishi Williams Issacs 安书成 Hiroshi Takeshima Jianjie Ma 徐学红 《中国细胞生物学学报》2015,(1):6-15
Ryanodine受体(ryanodine receptor,Ry R)是位于细胞内内质网/肌浆网膜上的钙离子释放通道蛋白。Ry R是由四个足状结构的亚单位组成的同源四聚体,每个亚单位大于550 k Da,四聚体的总分子量超过2 MDa,是迄今发现的内质网/肌浆网膜上最大的离子通道。哺乳动物有三种类型的Ry R,其中Ry R1主要分布在骨骼肌中,Ry R2首先发现于心肌,Ry R3主要在脑中有较多分布。Ry R钙离子释放通道在肌肉收缩、突触传递、激素分泌、蛋白折叠和程控性凋亡以及坏死等一系列以细胞功能为基础的生理过程中起着极其重要的作用,因而近些年在医学生物学和药学应用上都有极大的进展。该文就Ry R在机体中的分布、功能结构和调节因子等进行了介绍,其蛋白调节因子二氢吡啶受体(dihydropyridine receptor,DHPR)、钙调蛋白(Calmodulin)、隐钙素(calsequestrin)、FKBP(FK506-binding protein)家族蛋白和小分子调节因子咖啡因、离子等都是Ry R复合体行使细胞生理功能必不可少的因素。 相似文献
104.
Molecular spectrum of somaclonal variation in regenerated rice revealed by whole-genome sequencing 总被引:1,自引:0,他引:1
Miyao A Nakagome M Ohnuma T Yamagata H Kanamori H Katayose Y Takahashi A Matsumoto T Hirochika H 《Plant & cell physiology》2012,53(1):256-264
Somaclonal variation is a phenomenon that results in the phenotypic variation of plants regenerated from cell culture. One of the causes of somaclonal variation in rice is the transposition of retrotransposons. However, many aspects of the mechanisms that result in somaclonal variation remain undefined. To detect genome-wide changes in regenerated rice, we analyzed the whole-genome sequences of three plants independently regenerated from cultured cells originating from a single seed stock. Many single-nucleotide polymorphisms (SNPs) and insertions and deletions (indels) were detected in the genomes of the regenerated plants. The transposition of only Tos17 among 43 transposons examined was detected in the regenerated plants. Therefore, the SNPs and indels contribute to the somaclonal variation in regenerated rice in addition to the transposition of Tos17. The observed molecular spectrum was similar to that of the spontaneous mutations in Arabidopsis thaliana. However, the base change ratio was estimated to be 1.74 × 10(-6) base substitutions per site per regeneration, which is 248-fold greater than the spontaneous mutation rate of A. thaliana. 相似文献
105.
Miyazaki T Hashimoto K Uda A Sakagami H Nakamura Y Saito SY Nishi M Kume H Tohgo A Kaneko I Kondo H Fukunaga K Kano M Watanabe M Takeshima H 《FEBS letters》2006,580(17):4057-4064
By DNA cloning, we have identified the BSRP (brain-specific receptor-like proteins) family of three members in mammalian genomes. BSRPs were predominantly expressed in the soma and dendrites of neurons and localized in the endoplasmic reticulum (ER). Expression levels of BSRPs seemed to fluctuate greatly during postnatal cerebellar maturation. Triple-knockout mice lacking BSRP members exhibited motor discoordination, and Purkinje cells (PCs) were often innervated by multiple climbing fibers with different neuronal origins in the mutant cerebellum. Moreover, the phosphorylation levels of protein kinase Calpha (PKCalpha) were significantly downregulated in the mutant cerebellum. Because cerebellar maturation and plasticity require metabotropic glutamate receptor signaling and resulting PKC activation, BSRPs are likely involved in ER functions supporting PKCalpha activation in PCs. 相似文献
106.
Naito S Mochizuki H Yasuda T Mizuno Y Furusaka M Ikeda S Adachi T Shimizu HM Suzuki J Fujiwara S Okada T Nishikawa K Aoki S Wada K 《Biochemical and biophysical research communications》2006,339(2):717-725
Here, we illustrated that the morphological structures of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) variants and Parkinson's disease (PD) exhibit good pathological correlation by a small-angle neutron scattering (SANS). UCH-L1 is a neuro-specific multiple functional enzyme, deubiquitinating, ubiquityl ligase, and also involved in stabilization of mono-ubiquitin. To examine the relationship between multiple functions of UCH-L1 and the configuration of its variants [wild-type, I93M (linked to familial Parkinson's disease), and S18Y (linked to reduced risk of Parkinson's disease)], in this report, we proposed that these were all self-assembled dimers by an application of a rotating ellipsoidal model; the configurations of these dimers were quite different. The wild-type was a rotating ellipsoidal. The globular form of the monomeric component deformed by the I93M mutation. Conversely, the S18Y polymorphism promoted the globularity. Thus, the multiple functional balance is closely linked to the intermolecular interactions between the UCH-L1 monomer and the final dimeric configuration. 相似文献
107.
Cirp protects against tumor necrosis factor-alpha-induced apoptosis via activation of extracellular signal-regulated kinase 总被引:2,自引:0,他引:2
Sakurai T Itoh K Higashitsuji H Nonoguchi K Liu Y Watanabe H Nakano T Fukumoto M Chiba T Fujita J 《Biochimica et biophysica acta》2006,1763(3):290-295
Mild hypothermia shows protective effects on patients with brain damage and cardiac arrest. To elucidate the molecular mechanisms underlying these effects, we analyzed the effects of low culture temperature (32 degrees C) and cold-inducible RNA-binding protein (Cirp) expression on apoptosis in vitro. In BALB/3T3 cells treated with tumor necrosis factor (TNF)-alpha and cycloheximide, the down-shift in temperature from 37 degrees C to 32 degrees C increased the expression of Cirp and suppressed the apoptosis. Activation of caspase-8 was suppressed, and the level of phosphorylated extracellular signal-regulated kinase (ERK) was increased. Transduction of Cirp into the Cirp-deficient mouse fibroblasts increased the level of phosphorylated ERK and suppressed the TNF-alpha-induced apoptosis both at 37 degrees C and 32 degrees C. The ERK-specific inhibitor PD98059 decreased the cytoprotective effect of Cirp as well as that of low culture temperature. These data suggest that mild hypothermia protects cells from TNF-alpha-induced apoptosis, at least partly, via induction of Cirp, and that Cirp protects cells by activating the ERK pathway. 相似文献
108.
109.
Kaya Yoshida Hirohiko Okamura Daisuke Hinode Tatsuji Haneji 《Experimental cell research》2009,315(12):2105-3262
The double-stranded RNA-dependent protein kinase (PKR) plays a critical role in various biological responses including antiviral defense, cell differentiation, apoptosis, and tumorigenesis. In this study, we investigated whether PKR could affect the post-translational modifications of STAT1 protein and whether these modifications regulate osteoblast differentiation. We demonstrated that PKR was necessary for the ubiquitination of STAT1 protein. The expressions of bone-related genes such as type I collagen, integrin binding sialoprotein, osteopontin, and osterix were suppressed in osteoblasts lacking PKR activity. In contrast, the expressions of interleukin-6 and matrix metalloproteinases 8 and 13 increased in PKR-mutated osteoblasts. The expression and degradation of STAT1 protein were regulated by PKR in a SLIM-dependent pathway. Inhibition of SLIM by RNA interference resulted in the decreased activity of Runx2 in osteoblasts. Stimulation of interleukin-6 expression and suppression of alkaline phosphatase activity were regulated through by SLIM-dependent pathway. However, expressions of bone-related genes and MMPs were regulated by SLIM-independent pathway. Our present results suggest that the aberrant accumulation of STAT1 protein induced by loss of PKR regulate osteoblast differentiation through both SLIM/STAT1-dependent and -independent pathways. 相似文献
110.