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121.
Laude K Cai H Fink B Hoch N Weber DS McCann L Kojda G Fukai T Schmidt HH Dikalov S Ramasamy S Gamez G Griendling KK Harrison DG 《American journal of physiology. Heart and circulatory physiology》2005,288(1):H7-12
Protein levels and polymorphisms of p22(phox) have been suggested to modulate vascular NAD(P)H oxidase activity and vascular production of reactive oxygen species (ROS). We sought to determine whether increasing p22(phox) expression would alter vascular ROS production and hemodynamics by targeting p22(phox) expression to smooth muscle in transgenic (Tg) mice. Aortas of Tg(p22smc) mice had increased p22(phox) and Nox1 protein levels and produced more superoxide and H(2)O(2). Surprisingly, endothelium-dependent relaxation and blood pressure in Tg(p22smc) mice were normal. Aortas of Tg(p22smc) mice produced twofold more nitric oxide (NO) at baseline and sevenfold more NO in response to calcium ionophore as detected by electron spin resonance. Western blot analysis revealed a twofold increase in endothelial NO synthase (eNOS) protein expression in Tg(p22smc) mice. Both eNOS expression and NO production were normalized by infusion of the glutathione peroxidase mimetic ebselen or by crossing Tg(p22smc) mice with mice overexpressing catalase. We have previously found that NO stimulates extracellular superoxide dismutase (ecSOD) expression in vascular smooth muscle. In keeping with this, aortic segments from Tg(p22smc) mice expressed twofold more ecSOD, and chronic treatment with the NOS inhibitor N(G)-nitro-L-arginine methyl ester normalized this, suggesting that NO regulates ecSOD protein expression in vivo. These data indicate that chronic oxidative stress caused by excessive H(2)O(2) production evokes a compensatory response involving increased eNOS expression and NO production. NO in turn increases ecSOD protein expression and counterbalances increased ROS production leading to the maintenance of normal vascular function and hemodynamics. 相似文献
122.
Masaru Aoyagi Naomi Fukai Kazuo Ogami Mari Yamamoto Kiyotaka Yamamoto 《Journal of cellular physiology》1995,164(2):376-384
Platelet-derived growth factor (PDGF) is one of the major mitogens in serum to stimulate replication of human smooth muscle cells (SMCs) in culture. Previous studies using human fibroblasts failed to demonstrate changes in the receptor systems for growth factors during cellular senescence. We investigated the kinetics of 125I-PDGF(-BB) binding and down-regulation of the PDGF receptor in three human arterial SMC strains during cellular aging. The number of specific 125I-PDGF binding sites per cell increased slightly at a population doubling level (PDL) of 60%–80% of life span and then decreased at the PDL above 90%. The number of receptors per cell-surface area decreased with increasing in vitro age. The apparent Kd for the 125I-PDGF binding decreased with in vitro senescence. The internalization and degradation of 125I-PDGF per receptor were significantly reduced in senescent SMCs than young cells. Furthermore, down-regulation of the PDGF receptor was significantly greater in sensescent SMCs than young cells. Immunoblot studies demonstrated that changes in b?-subunit of the PDGF receptor accounted for those in the studies using 125I-PDGF and that tyrosine phosphorylation of the PDGF receptor was significantly greater in young SMCs than aged cells. Our results suggest that age-related changes in the receptor systems for PDGF may be important contributors to the failure of DNA synthesis in senescent SMCs. © 1995 Wiley-Liss, Inc. 相似文献
123.
Shintaro Kira Yuri Kumano Hirofumi Ukai Eigo Takeda Akira Matsuura Takeshi Noda 《Molecular biology of the cell》2016,27(2):382-396
TORC1 regulates cellular growth, metabolism, and autophagy by integrating various signals, including nutrient availability, through the small GTPases RagA/B/C/D in mammals and Gtr1/2 in budding yeast. Rag/Gtr is anchored to the lysosomal/vacuolar membrane by the scaffold protein complex Ragulator/Ego. Here we show that Ego consists of Ego1 and Ego3, and novel subunit Ego2. The ∆ego2 mutant exhibited only partial defects both in Gtr1-dependent TORC1 activation and Gtr1 localization on the vacuole. Ego1/2/3, Gtr1/2, and Tor1/Tco89 were colocalized on the vacuole and associated puncta. When Gtr1 was in its GTP-bound form and TORC1 was active, these proteins were preferentially localized on the vacuolar membrane, whereas when Gtr1 was in its GDP-bound form, they were mostly localized on the puncta. The localization of TORC1 to puncta was further facilitated by direct binding to Gtr2, which is involved in suppression of TORC1 activity. Thus regulation of TORC1 activity through Gtr1/Gtr2 is tightly coupled to the dynamic relocation of these proteins. 相似文献
124.
Competition in the temporal domain among neural activities phase-locked to subthreshold oscillations
Tomoki Fukai 《Biological cybernetics》1996,75(6):453-461
In the presence of a subthreshold membrane oscillation, analog information may be encoded in the timing of spike generation
phase-locked to the oscillation. With this spike timing neural code, a competitive network of inhibitory spiking neurons was
shown to achieve a novel timing mechanism of neural activity selection: the neurons had higher probabilities of becoming winners
if they were stimulated earlier in each oscillatory cycle. Here the timing mechanism and its robustness are studied both numerically
and analytically, and the conditions to yield a given number of winners (the inhibitory neurons that remain active after the
competition) are investigated. The analysis revealed that activity selection with a small number of winners is ensured for
broad ranges of values of the parameters such as the strength and time constant of inhibition. In particular, the number of
winners is almost unchanged for various timing differences between stimuli to different neurons. This implies that the timing
mechanism is useful for such biological information processing as requires perception of a relatively small number of significant
stimulus components.
Received: 24 January 1996 / Accepted in revised form: 24 July 1996 相似文献
125.
Hitoshi Tamiaki Kazuhiro Fukai Hideki Shimazu Katsunori Nishide Yutaka Shibata Shigeru Itoh Michio Kunieda 《Photochemical & photobiological sciences》2008,7(10):1231-1237
A heterodimer, where zinc pyropheophorbide-a was linked with zinc pyropheophorbide-d through ethylene glycol diester, was prepared, as well as the corresponding homodimers. The synthetic dimers were complexed with methanol in benzene to give folded dimers by mutual Zn...O(Me)-H...O=C13(1) bonding. Such complexes had furthest red (Qy) absorption bands at longer wavelengths than the monomeric species. These red-shifts were ascribable to excitonic coupling of the Qy transition states in the chlorin pi-pi stacking conformer. In the heterodimeric system, a minor band was observed at the shorter wavelength side of the main Qy band. This observation can be explained by an additional contribution of Qy vibronic state to the exciton-coupled states. Based on the experimental results, a pair of chlorophyll(Chl)-d with Chl-a as well as a Chl-d homopair were proposed as dimers in reaction centers of Chl-d dominating cyanobacteria. 相似文献
126.
Yusuke Sato Azusa Yoshikawa Hisatoshi Mimura Masami Yamashita Atsushi Yamagata Shuya Fukai 《The EMBO journal》2009,28(16):2461-2468
RAP80 has a key role in the recruitment of the Abraxas–BRCC36–BRCA1–BARD1 complex to DNA‐damage foci for DNA repair through specific recognition of Lys 63‐linked polyubiquitinated proteins by its tandem ubiquitin‐interacting motifs (UIMs). Here, we report the crystal structure of the RAP80 tandem UIMs (RAP80‐UIM1‐UIM2) in complex with Lys 63‐linked di‐ubiquitin at 2.2 Å resolution. The two UIMs, UIM1 and UIM2, and the α‐helical inter‐UIM region together form a continuous 60 Å‐long α‐helix. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties, respectively. Both UIM1 and UIM2 of RAP80 recognize an Ile 44‐centered hydrophobic patch on ubiquitin but neither UIM interacts with the Lys 63‐linked isopeptide bond. Our structure suggests that the inter‐UIM region forms a 12 Å‐long α‐helix that ensures that the UIMs are arranged to enable specific binding of Lys 63‐linked di‐ubiquitin. This was confirmed by pull‐down analyses using RAP80‐UIM1‐UIM2 mutants of various length inter‐UIM regions. Further, we show that the Epsin1 tandem UIM, which has an inter‐UIM region similar to that of RAP80‐UIM1‐UIM2, also selectively binds Lys 63‐linked di‐ubiquitin. 相似文献
127.
Amino acid requirements for the growth of Aedes albopictus, clone C6/36, cells and for the production of dengue (DEN) and Chikungunya (CHIK) viruses were examined by growing the cells or the viruses in media which were deprived of one of the 20 amino acids. Cell growth was markedly inhibited when cystine was omitted from the medium, and to a lesser extent by arginine deprivation. On the other hand, omission of alanine, asparagine, aspartic acid, and glutamic acid at the same time did not affect cell growth. Marked accumulation of alanine was observed in the medium when the cells were grown for 8 days in complete medium, with concomitant depletion of aspartic acid and glutamic acid. The production of CHIK virus was inhibited markedly by omission of cystine from the medium after virus infection, while the production of DEN viruses was more affected by glycine deprivation, although cystine deprivation also inhibited virus production to a lesser extent. On the other hand, production of CHIK and DEN viruses was not affected when alanine, asparagine, aspartic acid, and glutamic acid were omitted from the medium at the same time. 相似文献
128.
F Fukai M Kurano S Nishizawa Y Kiire T Nagai T Katayama 《Biochemistry international》1988,17(5):945-951
Reevaluation of the immunochemical relationships among the individual glutathione S-transferase (GST) isozymes (GSTs 1-1, 1-2, 2-2, 3-3, 3-4, 4-4, and GSTs with isoelectric points of 7.5 and 6.8) of rat liver cytosol was performed utilizing the immunoblot technique. As a result, we found that the respective isozymes of two isozyme classes of rat liver cytosol might possess a common epitope(s) which has been undetected by the Ouchterlony double-diffusion method. The assumption was further supported by the results of the effects of Fab' prepared from some anti-GST antibodies on the enzymatic activity of GSTs. 相似文献
129.
130.
Sato Y Yamagata A Goto-Ito S Kubota K Miyamoto R Nakada S Fukai S 《The Journal of biological chemistry》2012,287(31):25860-25868
UBC13 is the only known E2 ubiquitin (Ub)-conjugating enzyme that produces Lys-63-linked Ub chain with its cofactor E2 variant UEV1a or MMS2. Lys-63-linked ubiquitination is crucial for recruitment of DNA repair and damage response molecules to sites of DNA double-strand breaks (DSBs). A deubiquitinating enzyme OTUB1 suppresses Lys-63-linked ubiquitination of chromatin surrounding DSBs by binding UBC13 to inhibit its E2 activity independently of the isopeptidase activity. OTUB1 strongly suppresses UBC13-dependent Lys-63-linked tri-Ub production, whereas it allows di-Ub production in vitro. The mechanism of this non-canonical OTUB1-mediated inhibition of ubiquitination remains to be elucidated. Furthermore, the atomic level information of the interaction between human OTUB1 and UBC13 has not been reported. Here, we determined the crystal structure of human OTUB1 in complex with human UBC13 and MMS2 at 3.15 Å resolution. The presented atomic-level interactions were confirmed by surface-plasmon resonance spectroscopy with structure-based mutagenesis. The designed OTUB1 mutants cannot inhibit Lys-63-linked Ub chain formation in vitro and histone ubiquitination and 53BP1 assembly around DSB sites in vivo. Finally, we propose a model for how capping of di-Ub by the OTUB1-UBC13-MMS2/UEV1a complex efficiently inhibits Lys-63-linked tri-Ub formation. 相似文献