全文获取类型
收费全文 | 537篇 |
免费 | 31篇 |
出版年
2022年 | 4篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 10篇 |
2016年 | 10篇 |
2015年 | 22篇 |
2014年 | 20篇 |
2013年 | 41篇 |
2012年 | 41篇 |
2011年 | 45篇 |
2010年 | 20篇 |
2009年 | 23篇 |
2008年 | 31篇 |
2007年 | 34篇 |
2006年 | 33篇 |
2005年 | 35篇 |
2004年 | 31篇 |
2003年 | 24篇 |
2002年 | 27篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 8篇 |
1997年 | 15篇 |
1996年 | 6篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1985年 | 2篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
排序方式: 共有568条查询结果,搜索用时 31 毫秒
31.
32.
Yamamoto H Yamauchi E Taniguchi H Ono T Miyamoto E 《Archives of biochemistry and biophysics》2002,408(2):255-262
The paired helical filaments (PHF) found in Alzheimer's disease (AD) brain are composed mainly of the hyperphosphorylated form of microtubule-associated protein tau (PHF-tau). It is well known that tau is a good in vitro substrate for Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II). To establish the phosphorylation sites, the longest human tau (hTau40) was bacterially expressed and phosphorylated by CaM kinase II, followed by digestion with lysyl endoprotease. The digests were subjected to liquid chromatography/mass spectrometry. We found that 5 of 22 identified peptides were phosphorylated. From the tandem mass spectrometry, two phosphorylation sites (serines 262 and 356) were identified in the tubulin binding sites. When tau was phosphorylated by CaM kinase II, the binding of tau to taxol-stabilized microtubules was remarkably impaired. As both serines 262 and 356 are reportedly phosphorylated in PHF-tau, CaM kinase II may be involved in hyperphosphorylation of tau in AD brain. 相似文献
33.
Nosaka T Morita S Kitamura H Nakajima H Shibata F Morikawa Y Kataoka Y Ebihara Y Kawashima T Itoh T Ozaki K Senba E Tsuji K Makishima F Yoshida N Kitamura T 《Molecular and cellular biology》2003,23(8):2969-2980
Dorsoventral patterning depends on the local concentrations of the morphogens. Twisted gastrulation (TSG) regulates the extracellular availability of a mesoderm inducer, bone morphogenetic protein 4 (BMP-4). However, TSG function in vivo is still unclear. We isolated a TSG cDNA as a secreted molecule from the mouse aorta-gonad-mesonephros region. Here we show that TSG-deficient mice were born healthy, but more than half of the neonatal pups showed severe growth retardation shortly after birth and displayed dwarfism with delayed endochondral ossification and lymphopenia, followed by death within a month. TSG-deficient thymus was atrophic, and phosphorylation of SMAD1 was augmented in the thymocytes, suggesting enhanced BMP-4 signaling in the thymus. Since BMP-4 promotes skeletogenesis and inhibits thymus development, our findings suggest that TSG acts as both a BMP-4 agonist in skeletogenesis and a BMP-4 antagonist in T-cell development. Although lymphopenia in TSG-deficient mice would partly be ascribed to systemic effects of runtiness and wasting, our findings may also provide a clue for understanding the pathogenesis of human dwarfism with combined immunodeficiency. 相似文献
34.
Rosenberg EY Bertenthal D Nilles ML Bertrand KP Nikaido H 《Molecular microbiology》2003,48(6):1609-1619
AcrAB of Escherichia coli, an archetype among bacterial multidrug efflux pumps, exports an extremely wide range of substrates including solvents, dyes, detergents and antimicrobial agents. Its expression is regulated by three XylS/AraC family regulators, MarA, SoxS and Rob. Although MarA and SoxS regulation works by the alteration of their own expression levels, it was not known how Rob, which is constitutively expressed, exerts its regulatory action. We show here that the induction of the AcrAB efflux pump by decanoate and the more lipophilic unconjugated bile salts is mediated by Rob, and that the low-molecular-weight inducers specifically bind to the C-terminal, non-DNA-binding domain of Rob. Induction of Rob is not needed for induction of AcrAB, and we suggest that the inducers act by producing conformational alterations in pre-existing Rob, as was suggested recently (Rosner, Dangi, Gronenborn and Martin, J Bacteriol 184: 1407-1416, 2002). Decanoate and unconjugated bile salts, which are present in the normal habitat of E. coli, were further shown to make the bacteria more resistant to lipophilic antibiotics, at least in part because of the induction of the AcrAB efflux pump. Thus, it is likely that E. coli is protecting itself by the Rob-mediated upregulation of AcrAB against the harmful effects of bile salts and fatty acids in the intestinal tract. 相似文献
35.
We studied the synergistic effects of Japanese green tea extract (JGTE) and levofloxacin (LVFX) against enterohemorrhagic
Escherichia coli (EHEC) infection in a gnotobiotic mouse model. Mice fed on JGTE conferred a significant degree of protection against an oral
challenge with EHEC. Complete elimination of the bacteria from the mice, was however, difficult. The combination of JGTE and
LVFX increased the survival rate and reduced damage to target organs. Thus, dietary supplementation with JGTE improved the
therapeutic effects of antibiotic treatment.
Received: 28 July 2000 / Accepted: 19 September 2000 相似文献
36.
We have isolated a novel human cDNA coding for human salt-tolerant protein (HSTP), that is a homologue of the rat salt-tolerant
protein (STP) and may contribute to salt-induced hypertension by modulating renal cation transport. The nucleotide sequence
(1988 bp) of the HSTP cDNA contains an open reading frame encoding a polypeptide comprising 545 amino acids, two residues
fewer than the rat STP cDNA. The predicted amino acid sequence exhibits 92% identity to that of the rat protein. HSTP contains
predicted coiled-coil domains and Src Homology 3 domain, and shows a high degree of identity to CIP4 (Cdc42 target protein)
and human Trip 10 (thyroid-hormone receptor interacting protein). We have mapped the HSTPgene to human chromosome 19 by fluorescence in situhybridization.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
37.
Emiko Anegawa Nozomu Kotorii Yuji Ishimaru Masashi Okuro Noriaki Sakai Seiji Nishino 《PloS one》2015,10(12)
The purpose of this study is to clarify the effects of chronic powder diet feeding on sleep patterns and other physiological/anatomical changes in mice. C57BL/6 male mice were divided into two groups from weaning: a group fed with solid food (SD) and a group fed with powder food (PD), and sleep and physiological and anatomical changes were compared between the groups. PD exhibited less cranial bone structure development and a significant weight gain. Furthermore, these PD mice showed reduced number of neurogenesis in the hippocampus. Sleep analysis showed that PD induced attenuated diurnal sleep/wake rhythm, characterized by increased sleep during active period and decreased sleep during rest period. With food deprivation (FD), PD showed less enhancement of wake/locomotor activity compared to SD, indicating reduced food-seeking behavior during FD. These results suggest that powder feeding in mice results in a cluster of detrimental symptoms caused by abnormal energy metabolism and anatomical/neurological changes. 相似文献
38.
Emiko Matsunaga Yujiro Higuchi Kazuki Mori Nao Yairo Takuji Oka Saki Shinozuka Kosuke Tashiro Minoru Izumi Satoru Kuhara Kaoru Takegawa 《PloS one》2015,10(9)
β-D-galactofuranose (Galf) is a component of polysaccharides and glycoconjugates and its transferase has been well analyzed. However, no β-D-galactofuranosidase (Galf-ase) gene has been identified in any organism. To search for a Galf-ase gene we screened soil samples and discovered a strain, identified as a Streptomyces species by the 16S ribosomal RNA gene analysis, that exhibits Galf-ase activity for 4-nitrophenyl β-D-galactofuranoside (pNP-β-D-Galf) in culture supernatants. By draft genome sequencing of the strain, named JHA19, we found four candidate genes encoding Galf-ases. Using recombinant proteins expressed in Escherichia coli, we found that three out of four candidates displayed the activity of not only Galf-ase but also α-L-arabinofuranosidase (Araf-ase), whereas the other one showed only the Galf-ase activity. This novel Galf-specific hydrolase is encoded by ORF1110 and has an optimum pH of 5.5 and a Km of 4.4 mM for the substrate pNP-β-D-Galf. In addition, this enzyme was able to release galactose residue from galactomannan prepared from the filamentous fungus Aspergillus fumigatus, suggesting that natural polysaccharides could be also substrates. By the BLAST search using the amino acid sequence of ORF1110 Galf-ase, we found that there are homolog genes in both prokaryotes and eukaryotes, indicating that Galf-specific Galf-ases widely exist in microorganisms. 相似文献
39.
Kanazuru T Sato EF Nagata K Matsui H Watanabe K Kasahara E Jikumaru M Inoue J Inoue M 《Journal of microbiology (Seoul, Korea)》2010,48(6):778-783
Some gastrointestinal bacteria synthesize hydrogen (H2) by fermentation. Despite the presence of bactericidal factors in human saliva, a large number of bacteria also live in the
oral cavity. It has never been shown that oral bacteria also produce H2 or what role H2 might play in the oral cavity. It was found that a significant amount of H2 is synthesized in the oral cavity of healthy human subjects, and that its generation is enhanced by the presence of glucose
but inhibited by either teeth brushing or sterilization with povidone iodine. These observations suggest the presence of H2-generating bacteria in the oral cavity. The screening of commensal bacteria in the oral cavity revealed that a variety of
anaerobic bacteria generate H2. Among them, Klebsiella pneumoniae (K. pneumoniae) generated significantly large amounts of H2 in the presence of glucose. Biochemical analysis revealed that various proteins in K. pneumoniae are carbonylated under standard culture conditions, and that oxidative stress induced by the presence of Fe++ and H2O2 increases the number of carbonylated proteins, particularly when their hydrogenase activity is inhibited by KCN. Inhibition
of H2 generation markedly suppresses the growth of K. pneumoniae. These observations suggest that H2 generation and/or the reduction of oxidative stress is important for the survival and growth of K. pneumoniae in the oral cavity. 相似文献
40.