全文获取类型
收费全文 | 2740篇 |
免费 | 169篇 |
专业分类
2909篇 |
出版年
2022年 | 7篇 |
2021年 | 22篇 |
2020年 | 18篇 |
2019年 | 20篇 |
2018年 | 25篇 |
2017年 | 21篇 |
2016年 | 45篇 |
2015年 | 62篇 |
2014年 | 69篇 |
2013年 | 201篇 |
2012年 | 158篇 |
2011年 | 148篇 |
2010年 | 109篇 |
2009年 | 103篇 |
2008年 | 177篇 |
2007年 | 185篇 |
2006年 | 175篇 |
2005年 | 160篇 |
2004年 | 178篇 |
2003年 | 169篇 |
2002年 | 164篇 |
2001年 | 34篇 |
2000年 | 31篇 |
1999年 | 41篇 |
1998年 | 42篇 |
1997年 | 45篇 |
1996年 | 33篇 |
1995年 | 35篇 |
1994年 | 26篇 |
1993年 | 25篇 |
1992年 | 34篇 |
1991年 | 39篇 |
1990年 | 35篇 |
1989年 | 26篇 |
1988年 | 25篇 |
1987年 | 24篇 |
1986年 | 21篇 |
1985年 | 25篇 |
1984年 | 23篇 |
1983年 | 14篇 |
1982年 | 14篇 |
1981年 | 8篇 |
1980年 | 7篇 |
1979年 | 11篇 |
1977年 | 8篇 |
1976年 | 11篇 |
1975年 | 7篇 |
1974年 | 5篇 |
1973年 | 13篇 |
1972年 | 5篇 |
排序方式: 共有2909条查询结果,搜索用时 0 毫秒
991.
Toru Okamoto Yorihiro Nishimura Tohru Ichimura Kensuke Suzuki Tatsuo Miyamura Tetsuro Suzuki Kohji Moriishi Yoshiharu Matsuura 《The EMBO journal》2006,25(23):5634
Correction to: The EMBO Journal (2006) 25, 5015–5025. doi:10.1038/sj.emboj.7601367. 相似文献
992.
Four sesquiterpenoids--strobilols A (1), B (2), C (3), and D (4)--were isolated from the organic extracts of fruiting bodies of the edible mushroom Strobilurus ohshimae. Their structures were determined by spectroscopic methods. Compound 1 exhibited moderate activity against the brine shrimp Artemia salina. This paper is the first report on isolation of cadinane-type sesquiterpenoids from S. ohshimae. 相似文献
993.
Shibakusa T Mizunoya W Okabe Y Matsumura S Iwaki Y Okuno A Shibata K Inoue K Fushiki T 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,292(5):R1851-R1861
We have recently reported that inhibition of transforming growth factor (TGF)-beta in the brain reduced fat-related energy substrates concentrations in response to exercise. We investigated the relevance between the mobilization of fat-related energy substrates (nonesterified fatty acid and ketone bodies) during exercise and the effects of TGF-beta in the brain. Low-intensity exercise was simulated by contraction of the hindlimbs, induced by electrical stimulation at 2 Hz in anesthetized rats (Sim-Ex). As with actual exercise, it was confirmed that mobilization of carbohydrate-related energy substrates (glucose and lactic acid) occurred immediately after the onset of Sim-Ex, and mobilization of fat-related energy substrates followed thereafter. The timing of mobilization of fat-related substrates corresponded to that of the increase in TGF-beta in cerebrospinal fluid (CSF) in Sim-Ex. The level of TGF-beta in CSF significantly increased after 10 min of Sim-Ex and remained elevated until 30 min of Sim-Ex. Intracisternal administration of TGF-beta caused rapid mobilization of fat-related energy substrates. Meanwhile, there were no effects on the changes in carbohydrate-related substrates. The levels of catecholamines were slightly elevated after TGF-beta administration, and, although not significantly in statistical terms, we consider that at least a part of TGF-beta signal was transducted via the sympathetic nervous system because of these increases. These data indicate that TGF-beta in the brain is closely related to the mobilization of fat-related energy substrates during low-intensity exercise. We hypothesized that the central nervous system plays a role in the regulation of energy metabolism during low-intensity exercise and this may be mediated by TGF-beta. 相似文献
994.
995.
XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway 总被引:1,自引:0,他引:1
Rab GTPases are key regulators of intracellular membrane trafficking. We sought to elucidate the roles of Rab GTPases in Xenopus gastrulation, and found that a Xenopus homolog of Rab40 (XRab40) is required for normal gastrulation. XRab40 is localized at the Golgi apparatus and interacts with ElonginB/C and Cullin5 to form a ubiquitin ligase. XRab40/XCullin5 functions cooperatively and regulates the ubiquitination and localization of Rap2 GTPase. Furthermore, XRab40/XCullin5 regulates the membrane localization of Dishevelled (Dsh), a key signaling molecule in the Wnt pathway, through Rap2 and its effector Misshapen/Nck-interacting kinase (XMINK). XMINK interacts with Dsh, and is translocated to the plasma membrane by Wnt activation. We propose a novel signaling cascade consisting of XRab40/XCullin5, Rap2 and XMINK, which plays a crucial role in the regulation of the noncanonical Wnt pathway. 相似文献
996.
Membrane trafficking is one of the most important mechanisms involved in the establishment and maintenance of the forms and
functions of the cell. However, it is poorly understood in skeletal muscle cells. In this study, we have focused on vesicle-associated
membrane proteins (VAMPs), which are components of the vesicle docking and fusion complex, and have performed immunostaining
to investigate the expression of VAMPs in rat skeletal muscle tissue. We have found that VAMP2, but not VAMP1 or VAMP3, is
expressed in satellite cells. VAMP2 is also expressed in myofibers in the soleus muscle and nerve endings. This is consistent
with previous studies in which VAMP2 has been shown to regulate GLUT4 trafficking in slow-twitch myofibers in soleus muscle
and neurotransmitter release in nerve endings. As satellite cells are quiescent myogenic cells, the expression of VAMP2 has
further been examined in regenerating muscles after injury by the snake venom, cardiotoxin; we have observed enhanced expression
of VAMP2 in immature myotubes with a peak at 3 days after injury. Our findings suggest that VAMP2 plays roles in quiescent
satellite cells and is involved in muscle regeneration. The nature of the material transported in the VAMP2-bearing vesicles
in satellite cells and myotubes is still under investigation.
This work was supported by a research grant (17A-10) for nervous and mental disorders from the Ministry of Health, Labor,
and Welfare of Japan, and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan. 相似文献
997.
Galpha12 and Galpha13 transduce signals from G protein-coupled receptors to RhoA through RhoGEFs containing an RGS homology (RH) domain, such as p115 RhoGEF or leukemia-associated RhoGEF (LARG). The RH domain of p115 RhoGEF or LARG binds with high affinity to active forms of Galpha12 and Galpha13 and confers specific GTPase-activating protein (GAP) activity, with faster GAP responses detected in Galpha13 than in Galpha12. At the same time, Galpha13, but not Galpha12, directly stimulates the RhoGEF activity of p115 RhoGEF or nonphosphorylated LARG in reconstitution assays. In order to better understand the molecular mechanism by which Galpha13 regulates RhoGEF activity through interaction with RH-RhoGEFs, we sought to identify the region(s) of Galpha13 involved in either the GAP response or RhoGEF activation. For this purpose, we generated chimeras between Galpha12 and Galpha13 subunits and characterized their biochemical activities. In both cell-based and reconstitution assays of RhoA activation, we found that replacing the carboxyl-terminal region of Galpha12 (residues 267-379) with that of Galpha13 (residues 264-377) conferred gain-of-function to the resulting chimeric subunit, Galpha12C13. The inverse chimera, Galpha13C12, exhibited basal RhoA activation which was similar to Galpha12. In contrast to GEF assays, GAP assays showed that Galpha12C13 or Galpha13C12 chimeras responded to the GAP activity of p115 RhoGEF or LARG in a manner similar to Galpha12 or Galpha13, respectively. We conclude from these results that the carboxyl-terminal region of Galpha13 (residues 264-377) is essential for its RhoGEF stimulating activity, whereas the amino-terminal alpha helical and switch regions of Galpha12 and Galpha13 are responsible for their differential GAP responses to the RH domain. 相似文献
998.
Hachiya S Kawabata F Ohnuki K Inoue N Yoneda H Yazawa S Fushiki T 《Bioscience, biotechnology, and biochemistry》2007,71(3):671-676
We investigated the changes in autonomic nervous activity, body temperature, blood pressure (BP), and heart rate (HR) after intake of the non-pungent pepper CH-19 Sweet and of hot red pepper in humans to elucidate the mechanisms of diet-induced thermogenesis (DIT) due to CH-19 Sweet. We found that CH-19 Sweet activates the sympathetic nervous system (SNS) and enhances thermogenesis as effectively as hot red pepper, ant that the heat loss effect due to CH-19 Sweet is weaker than that due to hot red pepper. Furthermore, we found that intake of CH-19 Sweet does not affect systolic BP or HR, while hot red pepper transiently elevates them. These results indicate that DIT due to CH-19 Sweet can be induced via the activation of SNS as well as hot red pepper, but that the changes in BP, HR, and heat loss effect are different between these peppers. 相似文献
999.
Yoshioka M Murayama Y Miwa T Miura K Takata M Yokoyama T Nishizawa K Mohri S 《Bioscience, biotechnology, and biochemistry》2007,71(10):2565-2568
Prions, infectious agents causing transmissible spongiform encephalopathy, retain infectivity even after undergoing routine sterilization processes. We found that MSK103 protease, identified in our previous study, effectively reduces infectivity and the level of misfolded isoform of the prion protein in scrapie-infected brain homogenates in the presence of SDS. The treatment therefore can be applied to the decontamination of thermolabile instruments. 相似文献
1000.
Hirayasu H Yoshikawa Y Tsuzuki S Fushiki T 《Bioscience, biotechnology, and biochemistry》2007,71(1):234-237
In the large-intestinal mucosae of rats orally administered dextran sulfate sodium, which induces an enteritis resembling ulcerative colitis (UC), the activity for granzyme A, a lymphocyte tryptase, increased at an earlier stage than that at which UC markers (growth-regulated gene product/cytokine-induced neutrophil chemoattractant-1 and caspase-3) increased. This suggests involvement of the enzyme in the exacerbation and perpetuation of enteritis. 相似文献