全文获取类型
收费全文 | 673篇 |
免费 | 35篇 |
国内免费 | 2篇 |
出版年
2021年 | 2篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 13篇 |
2014年 | 9篇 |
2013年 | 114篇 |
2012年 | 29篇 |
2011年 | 31篇 |
2010年 | 21篇 |
2009年 | 17篇 |
2008年 | 26篇 |
2007年 | 32篇 |
2006年 | 30篇 |
2005年 | 38篇 |
2004年 | 38篇 |
2003年 | 32篇 |
2002年 | 26篇 |
2001年 | 16篇 |
2000年 | 24篇 |
1999年 | 20篇 |
1998年 | 8篇 |
1997年 | 9篇 |
1996年 | 11篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 7篇 |
1992年 | 9篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 15篇 |
1988年 | 13篇 |
1987年 | 9篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1963年 | 2篇 |
1962年 | 4篇 |
1956年 | 1篇 |
排序方式: 共有710条查询结果,搜索用时 15 毫秒
81.
Fujikane R Komori K Shinagawa H Ishino Y 《The Journal of biological chemistry》2005,280(13):12351-12358
To identify the branch migration activity in archaea, we fractionated Pyrococcus furiosus cell extracts by several chromatography and assayed for ATP-dependent resolution of synthetic Holliday junctions. The target activity was identified in the column fractions, and the optimal reaction conditions for the branch migration activity were determined using the partially purified fraction. We successfully cloned the corresponding gene by screening a heat-stable protein library made by P. furiosus genomic DNA. The gene, hjm (Holliday junction migration), encodes a protein composed of 720 amino acids. The Hjm protein is conserved in Archaea and belongs to the helicase superfamily 2. A homology search revealed that Hjm shares sequence similarity with the human PolTheta, HEL308, and Drosophila Mus308 proteins, which are involved in a DNA repair, whereas no similar sequences were found in bacteria and yeast. The Hjm helicase may play a central role in the repair systems of organisms living in extreme environments. 相似文献
82.
Calcium-induced structural transition in the amino-terminal domain of troponin C (TnC) triggers skeletal and cardiac muscle contraction. The salient feature of this structural transition is the movement of the B and C helices, which is termed the "opening" of the N-domain. This movement exposes a hydrophobic region, allowing interaction with the regulatory domain of troponin I (TnI) as can be seen in the crystal structure of the troponin ternary complex [Takeda, S., Yamashita, A., Maeda, K., and Maeda, Y. (2003) Nature 424, 35-41]. In contrast to skeletal TnC, Ca(2+)-binding site I (an EF-hand motif that consists of an A helix-loop-B helix motif) is inactive in cardiac TnC. The question arising from comparisons with skeletal TnC is how both helices move according to Ca(2+) binding or interact with TnI in cardiac TnC. In this study, we examined the Ca(2+)-induced movement of the B and C helices relative to the D helix in a cardiac TnC monomer state and TnC-TnI binary complex by means of site-directed spin labeling electron paramagnetic resonance (EPR). Doubly spin-labeled TnC mutants were prepared, and the spin-spin distances were estimated by analyzing dipolar interactions with the Fourier deconvolution method. An interspin distance of 18.4 A was estimated for mutants spin labeled at G42C on the B helix and C84 on the D helix in a Mg(2+)-saturated monomer state. The interspin distance between Q58C on the C helix and C84 on the D helix was estimated to be 18.3 A under the same conditions. Distance changes were observed by the addition of Ca(2+) ions and the formation of a complex with TnI. Our data indicated that the C helix moved away from the D helix in a distinct Ca(2+)-dependent manner, while the B helix did not. A movement of the B helix by interaction with TnI was observed. Both Ca(2+) and TnI were also shown to be essential for the full opening of the N-domain in cardiac TnC. 相似文献
83.
Nagase T Shimozawa N Takemoto Y Suzuki Y Komori M Kondo N 《Biochimica et biophysica acta》2004,1671(1-3):26-33
In subjects with Zellweger syndrome, the most severe phenotype of peroxisomal biogenesis disorder, brain abnormalities include cortical dysplasia, neuronal heterotopia, and dysmyelination. To clarify the relationship between the lack of peroxisomes and neuronal abnormalities, we investigated peroxisomal localization in the mouse cerebellum, using double immunofluorescent staining for peroxisomal proteins. On immunostaining for peroxisomal matrix protein, while there are few peroxisomes in Purkinje cells, many locate in astroglia, especially soma of Bergmann glia. Clusters of peroxisomes were seen on the inferior side of the Purkinje cell layer in mice on postnatal days 3-5, and with time there was a shift to the superior side. The peroxisomal punctate pattern was seen to be radial and co-localized with Bergmann glial fibers. In cultured cells from the mouse cerebellum, peroxisomes were few in Purkinje cells, whereas many were evident in glial fibrillary acidic protein-positive cells. On the other hand, on immunostaining for peroxisomal membrane protein Pex14p, many particles were seen in Purkinje cells during all developmental stages, which means Purkinje cells possessed empty peroxisomal structures similar to findings of fibroblasts from the Zellweger patients. As peroxisomes in glial cells may control the development of neurons, the neuron-glial interaction and mechanisms of developing central nervous systems deserve ongoing attention. 相似文献
84.
85.
Komori K Hidaka M Horiuchi T Fujikane R Shinagawa H Ishino Y 《The Journal of biological chemistry》2004,279(51):53175-53185
Blockage of replication fork progression often occurs during DNA replication, and repairing and restarting stalled replication forks are essential events in all organisms for the maintenance of genome integrity. The repair system employs processing enzymes to restore the stalled fork. In Archaea Hef is a well conserved protein that specifically cleaves nicked, flapped, and fork-structured DNAs. This enzyme contains two distinct domains that are similar to the DEAH helicase family and XPF nuclease superfamily proteins. Analyses of truncated mutant proteins consisting of each domain revealed that the C-terminal nuclease domain independently recognized and incised fork-structured DNA. The N-terminal helicase domain also specifically unwound fork-structured DNA and Holliday junction DNA in the presence of ATP. Moreover, the endonuclease activity of the whole Hef protein was clearly stimulated by ATP hydrolysis catalyzed by the N-terminal domain. These enzymatic properties suggest that Hef efficiently resolves stalled replication forks by two steps, which are branch point transfer to the 5'-end of the nascent lagging strand by the N-terminal helicase followed by template strand incision for leading strand synthesis by the C-terminal endonuclease. 相似文献
86.
Nakamura A Komori H Kobayashi G Kita A Wada C Miki K 《Biochemical and biophysical research communications》2004,315(1):10-15
The initiator protein RepE of the mini-F plasmid in Escherichia coli plays an essential role in DNA replication, which is regulated by the molecular chaperone-dependent oligomeric state (monomer or dimer). Crosslinking, ultracentrifugation, and gel filtration analyses showed that the solely expressed N-terminal domain (residues 1-144 or 1-152) exists in the dimeric state as in the wild-type RepE protein. This result indicates that the N-terminal domain functions as a dimerization domain of RepE and might be important for the interaction with the molecular chaperones. The N-terminal domain dimer has been crystallized in order to obtain structural insight into the regulation of the monomer/dimer conversion of RepE. 相似文献
87.
In mammalian cells, several observations indicate not only that phosphate transport probably regulates local inorganic phosphate (Pi) concentration, but also that Pi affects normal cellular metabolism, which in turn regulates apoptosis and the process of mineralization. To elucidate how extracellular Pi regulates cellular functions of pre-osteoblastic cells, we investigated the expression of type III sodium (Na)-dependent Pi transporters in rat bone marrow stromal cells and ROB-C26 pre-osteoblastic cells. The mRNA expression level of gibbon ape leukemia virus receptor (Glvr)-2 was increased by the addition of Pi in rat bone marrow stromal cells, but not in ROB-C26 or normal rat kidney (NRK) cells. In contrast, the level of Glvr-1 mRNA was not altered by the addition of extracellular Pi in these cells. The induction of Glvr-2 mRNA by Pi was inhibited in the presence of cycloheximide (CHX). Moreover, mitogen-activated protein kinase (MEK) /extracellular-signal-regulated kinase (ERK) pathway inhibitors; U0126 (1.4-diamino-2, 3-dicyano-1, 4-bis [2-amino-phenylthio] butadiene) and PD98059 (2'-Amino-3'-methoxyflavone) inhibited inducible Glvr-2 mRNA expression, but p38 MEK inhibitor SB203580 [4-(4'-fluorophenyl)-2-(4'-methyl-sulfinylphenyl)-5-(4'pyridyl) imidazole] did not inhibit the induction of Glvr-2 mRNA expression, suggesting that extracellular Pi regulates de novo protein synthesis and MEK/ERK activity in rat bone marrow stromal cells, and through these, induction of Glvr-2 mRNA. Although Pi also induced osteopontin mRNA expression in rat bone marrow stromal cells but not in ROB-C26 and NRK cells, changes in cell viability with the addition of Pi were similar in both cell types. These data indicate that extracellular Pi regulates Glvr-2 mRNA expression, provide insights into possible mechanisms whereby Pi may regulate protein phosphorylation, and suggest a potential role for the Pi transporter in rat bone marrow stromal cells. 相似文献
88.
Head module control of mediator interactions 总被引:5,自引:0,他引:5
Takagi Y Calero G Komori H Brown JA Ehrensberger AH Hudmon A Asturias F Kornberg RD 《Molecular cell》2006,23(3):355-364
89.
90.
Naoki Shibata Hiroko Tamagaki Naoki Hieda Keita Akita Hirofumi Komori Yasuhito Shomura Shin-ichi Terawaki Koichi Mori Noritake Yasuoka Yoshiki Higuchi Tetsuo Toraya 《The Journal of biological chemistry》2010,285(34):26484-26493
N-terminal truncation of the Escherichia coli ethanolamine ammonia-lyase β-subunit does not affect the catalytic properties of the enzyme (Akita, K., Hieda, N., Baba, N., Kawaguchi, S., Sakamoto, H., Nakanishi, Y., Yamanishi, M., Mori, K., and Toraya, T. (2010) J. Biochem. 147, 83–93). The binary complex of the truncated enzyme with cyanocobalamin and the ternary complex with cyanocobalamin or adeninylpentylcobalamin and substrates were crystallized, and their x-ray structures were analyzed. The enzyme exists as a trimer of the (αβ)2 dimer. The active site is in the (β/α)8 barrel of the α-subunit; the β-subunit covers the lower part of the cobalamin that is bound in the interface of the α- and β-subunits. The structure complexed with adeninylpentylcobalamin revealed the presence of an adenine ring-binding pocket in the enzyme that accommodates the adenine moiety through a hydrogen bond network. The substrate is bound by six hydrogen bonds with active-site residues. Argα160 contributes to substrate binding most likely by hydrogen bonding with the O1 atom. The modeling study implies that marked angular strains and tensile forces induced by tight enzyme-coenzyme interactions are responsible for breaking the coenzyme Co–C bond. The coenzyme adenosyl radical in the productive conformation was modeled by superimposing its adenine ring on the adenine ring-binding site followed by ribosyl rotation around the N-glycosidic bond. A major structural change upon substrate binding was not observed with this particular enzyme. Gluα287, one of the substrate-binding residues, has a direct contact with the ribose group of the modeled adenosylcobalamin, which may contribute to the substrate-induced additional labilization of the Co–C bond. 相似文献