全文获取类型
收费全文 | 2772篇 |
免费 | 195篇 |
专业分类
2967篇 |
出版年
2022年 | 15篇 |
2021年 | 19篇 |
2020年 | 13篇 |
2019年 | 20篇 |
2018年 | 20篇 |
2017年 | 19篇 |
2016年 | 37篇 |
2015年 | 57篇 |
2014年 | 75篇 |
2013年 | 143篇 |
2012年 | 118篇 |
2011年 | 116篇 |
2010年 | 69篇 |
2009年 | 81篇 |
2008年 | 131篇 |
2007年 | 105篇 |
2006年 | 129篇 |
2005年 | 117篇 |
2004年 | 135篇 |
2003年 | 125篇 |
2002年 | 103篇 |
2001年 | 115篇 |
2000年 | 125篇 |
1999年 | 112篇 |
1998年 | 38篇 |
1997年 | 40篇 |
1996年 | 44篇 |
1995年 | 34篇 |
1994年 | 35篇 |
1993年 | 33篇 |
1992年 | 71篇 |
1991年 | 53篇 |
1990年 | 51篇 |
1989年 | 41篇 |
1988年 | 62篇 |
1987年 | 54篇 |
1986年 | 36篇 |
1985年 | 37篇 |
1984年 | 43篇 |
1983年 | 40篇 |
1982年 | 21篇 |
1981年 | 17篇 |
1980年 | 20篇 |
1979年 | 25篇 |
1978年 | 19篇 |
1977年 | 14篇 |
1975年 | 18篇 |
1974年 | 15篇 |
1969年 | 15篇 |
1968年 | 18篇 |
排序方式: 共有2967条查询结果,搜索用时 8 毫秒
51.
Kenichiro Kinouchi Atsuhiro Ichihara Motoaki Sano Ge-Hong Sun-Wada Yoh Wada Hiroki Ochi Toru Fukuda Kanako Bokuda Hideaki Kurosawa Naohiro Yoshida Shu Takeda Keiichi Fukuda Hiroshi Itoh 《PloS one》2013,8(11)
The ATPase 6 accessory protein 2 (ATP6AP2)/(pro)renin receptor (PRR) is essential for the biogenesis of active vacuolar H+-ATPase (V-ATPase). Genetic deletion of ATP6AP2/PRR causes V-ATPase dysfunction and compromises vesicular acidification. Here, we characterized the domains of ATP6AP2/PRR involved in active V-ATPase biogenesis. Three forms of ATP6AP2/PRR were found intracellularly: full-length protein and the N- and C-terminal fragments of furin cleavage products, with the N-terminal fragment secreted extracellularly. Genetic deletion of ATP6AP2/PRR did not affect the protein stability of V-ATPase subunits. The extracellular domain (ECD) and transmembrane domain (TM) of ATP6AP2/PRR were indispensable for the biogenesis of active V-ATPase. A deletion mutant of ATP6AP2/PRR, which lacks exon 4-encoded amino acids inside the ECD (Δ4M) and causes X-linked mental retardation Hedera type (MRXSH) and X-linked parkinsonism with spasticity (XPDS) in humans, was defective as a V-ATPase-associated protein. Prorenin had no effect on the biogenesis of active V-ATPase. The cleavage of ATP6AP2/PRR by furin seemed also dispensable for the biogenesis of active V-ATPase. We conclude that the N-terminal ECD of ATP6AP2/PRR, which is also involved in binding to prorenin or renin, is required for the biogenesis of active V-ATPase. The V-ATPase assembly occurs prior to its delivery to the trans-Golgi network and hence shedding of ATP6AP2/PRR would not affect the biogenesis of active V-ATPase. 相似文献
52.
Dimethyl fumarate inhibits osteoclasts via attenuation of reactive oxygen species signalling by augmented antioxidation 下载免费PDF全文
53.
54.
Altered sialylation of glycosphingolipids is observed in cancer as a ubiquitous phenotype, leading to the appearance of tumor-associated antigens, aberrant adhesion and disturbance of transmembrane signaling. To understand the pathological significance of aberrant alterations of gangliosides in cancer, our studies have been focused on sialidase, which is responsible for the removal of sialic acids from glycoproteins and glycolipids. Among human sialidases so far identified, sialidase NEU3 is a key enzyme for ganglioside degradation because of its uniqueness both in its localization in the plasma membrane and in specifically hydrolyzing gangliosides. NEU3 is markedly up-regulated in many types of cancers including colon and renal carcinomas and suppresses apoptosis of cancer cells. The present paper briefly summarizes our recent results on the sialidase alterations and their significance in cancer. NEU3 is indeed closely related to malignancy and thus may be a potential target for cancer diagnosis and therapy. 相似文献
55.
Kato Ryoichi; Takatsuna Sachiko; Wada Tsuyoshi; Narihara Yumi; Suzuki Takashi 《Plant & cell physiology》1996,37(5):667-672
Five-mm sections of elongation zones of Zea mesocotyls wereincubated for designated periods with various concentrationsof IAA. In vitro protein phosphorylation in the soluble fraction(85,000 x g supernatant) prepared from the sections was analyzedby sodium dodecyl sulfate-polyacrylamide gel electrophoresis.The phosphorylation of proteins in the soluble fraction thathad been prepared from sections incubated for 20 min in thepresence of 10{small tilde}s M IAA was greater than that inthe sections incubated for 20 min without IAA. The amount ofphosphorylation of proteins per protein became higher when higherconcentrations increased (10{small tilde}810{small tilde}5M).The growth of sections incubated in the presence of 10{smalltilde}8 M IAA or higher concentrations was greater than thatof sections incubated in the absence of IAA. The promotion ofgrowth by IAA was greater at higher concentrations of IAA. Proteinsin the soluble fraction, prepared from sections incubated for20 min in the presence of 10{small tilde}5 M IAA, were phosphorylatedin the presence of either 10 fM cAMP, 10 µM cGMP, 100µM W-7, 100 µM W-5, 20 µM H-7 or 20 µMHA1004. The calmodulin antagonist, W-7, and the inhibitor ofprotein kinase C, H-7, inhibited the phosphorylation of proteinsstimulated by incubation with IAA. These results suggest thatIAA promotes cell elongation via protein phosphorylation thatdepends on calmodulin-dependent protein kinase and protein kinaseC. (Received November 29, 1995; Accepted May 20, 1996) 相似文献
56.
In plant cells, the pyruvate dehydrogenase (PDH) complex that requires lipoic acid as an essential coenzyme is located in plastids and mitochondria. The enzyme complex has to be lipoylated in both organelles. However, the lipoyltransferase located in plastids has not been reported. In this study, an Arabidopsis thaliana LIP2p cDNA for a lipoyltransferase located in plastids has been identified. We have shown that this cDNA encodes a lipoyltransferase by demonstrating its ability to complement an Escherichia coli mutant lacking lipoyltransferase activity, and that LIP2p is targeted into chloroplasts. These findings suggest that LIP2p is located in plastids and responsible for lipoylation of the plastidial PDH complex. 相似文献
57.
58.
Hiroshi Tamura Noriko Wada Hong Zhang Hironari Unrin Takafumi Watanabe Tetsuya Suga 《Cell biochemistry and biophysics》2000,32(1-3):325-327
Peroxisome proliferators (PPs) are nongenotoxic compounds causing the emergence of hepatocellular carcinoma in rodents, but
the mechanisms of the hepatocarcinogenesis have been unclear. The authors examined the changes in phosphorylation of nuclear
proteins after treatment with (4-chloro-6-[2,3-xylidino]-2-pyrimidinylthio) acetic acid (Wy-14,643). Wy-14,643 (0.1% w/w in
diet) was given orally to male F-344 rats for up to 80 wk. In the hepatocarcinomas induced by Wy-14,643, phosphorylation of
13 kDa nuclear protein (NP 13), which was resistant to alkaline treatment, was significantly increased. NP 13 phosphorylation
gradually increased, dependent on treatment period. Furthermore, in the hepatocarcinomas induced by other PP, di(2-ethylhexyl)phthalate,
increase in NP13-phospholyration was also observed. Therefore, NP 13-phospholyration may relate to development of preneoplastic
or neoplastic lesions induced by PPs. 相似文献
59.
Cloning of a rat glia maturation factor-gamma (rGMFG) cDNA and expression of its mRNA and protein in rat organs 总被引:4,自引:0,他引:4
Tsuiki H Asai K Yamamoto M Fujita K Inoue Y Kawai Y Tada T Moriyama A Wada Y Kato T 《Journal of biochemistry》2000,127(3):517-523
We isolated a rat glia maturation factor-gamma(rGMFG) cDNA and examined the tissue distribution of GMFG in rat by Northern and Western blot analyses. Sequence analysis of the entire cDNA revealed an open reading frame of 426 nucleotides with a deduced protein of 142 amino acid residues. The deduced amino acid sequence of the putative product is highly homologous (78.9%) to rat glia maturation factor-beta (rGMFB). Northern blot analysis indicated that a 0.9-kb mRNA is predominantly expressed in rat thymus, testis, and spleen. GMFG showed a different tissue distribution from GMFB, being present predominantly in proliferative and differentiative organs. 相似文献