全文获取类型
收费全文 | 415篇 |
免费 | 53篇 |
专业分类
468篇 |
出版年
2022年 | 3篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 13篇 |
2013年 | 15篇 |
2012年 | 25篇 |
2011年 | 19篇 |
2010年 | 9篇 |
2009年 | 15篇 |
2008年 | 17篇 |
2007年 | 14篇 |
2006年 | 23篇 |
2005年 | 27篇 |
2004年 | 20篇 |
2003年 | 21篇 |
2002年 | 22篇 |
2001年 | 26篇 |
2000年 | 31篇 |
1999年 | 19篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1989年 | 9篇 |
1988年 | 5篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1965年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有468条查询结果,搜索用时 13 毫秒
61.
Hino T Yokota T Ito S Nishina K Kang YS Mori S Hori S Kanda T Terasaki T Mizusawa H 《Biochemical and biophysical research communications》2006,340(1):263-267
Brain capillary endothelial cells (BCECs) play an important role in blood-brain barrier (BBB) functions and pathophysiologic mechanisms in brain ischemia and inflammation. We try to suppress gene expression in BCECs by intravenous application of small interfering RNA (siRNA). After injection of large dose siRNA with hydrodynamic technique to mouse, suppression of endogenous protein and the BBB function of BCECs was investigated. The brain-to-blood transport function of organic anion transporter 3 (OAT3) that expressed in BCECs was evaluated by Brain Efflux Index method in mouse. The siRNA could be delivered to BCECs and efficiently inhibited endogenously expressed protein of BCECs. The suppression effect of siRNA to OAT3 is enough to reduce the brain-to-blood transport of OAT3 substrate, benzylpenicillin at BBB. The in vivo siRNA-silencing method with hydrodynamic technique may be useful for the study of BBB function and gene therapy targeting BCECs. 相似文献
62.
Kusano S Kukimoto-Niino M Hino N Ohsawa N Okuda K Sakamoto K Shirouzu M Shindo T Yokoyama S 《Protein science : a publication of the Protein Society》2012,21(2):199-210
The calcitonin receptor-like receptor (CRLR), a class B GPCR, forms a heterodimer with receptor activity-modifying protein 2 (RAMP2), and serves as the adrenomedullin (AM) receptor to control neovascularization, while CRLR and RAMP1 form the calcitonin gene-related peptide (CGRP) receptor. Here, we report the crystal structures of the RAMP2 extracellular domain alone and in the complex with the CRLR extracellular domain. The CRLR-RAMP2 complex exhibits several intermolecular interactions that were not observed in the previously reported CRLR-RAMP1 complex, and thus the shape of the putative ligand-binding pocket of CRLR-RAMP2 is distinct from that of CRLR-RAMP1. The CRLR-RAMP2 interactions were confirmed for the full-length proteins on the cell surface by site-specific photo-crosslinking. Mutagenesis revealed that AM binding requires RAMP2 residues that are not conserved in RAMP1. Therefore, the differences in both the shapes and the key residues of the binding pocket are essential for the ligand specificity. 相似文献
63.
Jiang R Wang S Takahashi K Fujita H Fruci CR Breyer MD Harris RC Takahashi T 《Genesis (New York, N.Y. : 2000)》2012,50(9):685-692
Mice with endothelial nitric oxide synthase (eNOS) deletions have defined the crucial role of eNOS in vascular development, homeostasis, and pathology. However, cell specific eNOS function has not been determined, although an important role of eNOS has been suggested in multiple cell types. Here, we have generated a floxed eNOS allele in which exons 9–12, encoding the sites essential to eNOS activity, are flanked with loxP sites. Mice homozygous for the floxed allele showed normal eNOS protein levels and no overt phenotype. Conversely, homozygous mice with Cre‐deleted alleles displayed truncated eNOS protein, lack of vascular NO production, and exhibited similar phenotype to eNOS knockout mice, including hypertension, low heart rate, and focal renal scarring. These findings demonstrate that the floxed allele is normal and it can be converted to a non‐functional eNOS allele through Cre recombination. This mouse will allow time‐ and cell‐specific eNOS deletion. genesis 50:685–692, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
64.
M Hara-Yokoyama M Kukimoto-Niino K Terasawa S Harumiya KA Podyma-Inoue N Hino K Sakamoto S Itoh N Hashii Y Hiruta N Kawasaki C Mishima-Tsumagari Y Kaitsu T Matsumoto M Wakiyama M Shirouzu T Kasama H Takayanagi N Utsunomiya-Tate K Takatsu T Katada Y Hirabayashi S Yokoyama M Yanagishita 《Structure (London, England : 1993)》2012,20(9):1585-1595
The leukocyte cell-surface antigen CD38 is the major nicotinamide adenide dinucleotide glycohydrolase in mammals, and its ectoenzyme activity is involved in calcium mobilization. CD38 is also a raft-dependent signaling molecule. CD38 forms a tetramer on the cell surface, but the structural basis and the functional significance of tetramerization have remained unexplored. We identified the interfaces contributing to the homophilic interaction of mouse CD38 by site-specific crosslinking on the cell surface with an expanded genetic code, based on a crystallographic analysis. A combination of the three interfaces enables CD38 to tetramerize: one interface involving the juxtamembrane α-helix is responsible for the formation of the core dimer, which is further dimerized via the other two interfaces. This dimerization of dimers is required for the catalytic activity and the localization of CD38 in membrane rafts. The glycosylation prevents further self-association of the tetramer. Accordingly, the tetrameric interaction underlies the multifaceted actions of CD38. 相似文献
65.
66.
Misumi S Eto A Mitsumata R Yamada M Takamune N Shoji S 《Biochemical and biophysical research communications》2008,377(2):617-621
Our previous study demonstrated that the immunization with a cycloimmunogen derived from extracellular loop-2 (ECL-2) of CCR5 (cDDR5) attenuated acute phase of CCR5-tropic simian-human immunodeficiency virus (SHIV)SF162P3 replication in vivo. Although the study showed that the antisera raised against cDDR5 reacted with cell-expressed CCR5, we have not yet demonstrated whether the antisera can react with virion-incorporated CCR5. Here, we show that rhesus cDDR5 (rcDDR5)-specific antibodies react with not only cell-expressed but also virion-incorporated simian CCR5s (siCCR5s), but may predominantly exert their inhibitory effects on simian immunodeficiency virus (SIV) infection by the binding of cell-expressed rather than virion-incorporated CCR5s. These results suggest that the virion-incorporated CCR5 may contribute to the reactivation of the anti-rcDDR5 antibody-producing B-cells by SIV particles after rcDDR5 immunization, although the binding of anti-rcDDR5 antibody to virion-incorporated CCR5 results in a partial inhibitory effect on SIV infection. 相似文献
67.
Suzuki T Das SK Inoue H Kazami M Hino O Kobayashi T Yeung RS Kobayashi K Tadokoro T Yamamoto Y 《Biochemical and biophysical research communications》2008,368(1):132-137
The products of the TSC1 (hamartin) and TCS2 (tuberin) tumor suppressor genes negatively regulate cell growth by inhibiting mTOR signaling. Recent research has led to the postulation that tuberin and/or hamartin are involved in tumor migration, presumably through Rho activation. Here we show that LEF-8 cells, which contain a Y1571 missense mutation in tuberin, express higher Rac1 activity than tuberin negative and positive cells. We also provide evidence of obvious lamellipodia formation in LEF-8 cells. Since the production of TSC2Y1571H cannot form a hetero-complex with hamartin, we further analyzed another mutant, TSC2R611Q, which also lacks the ability to form a complex with hamartin. Introducing both forms of mutated TSC2 into COS-1 cells increased Rac1 activity as well as cell motility. We also found these two mutants interacted with Rac1. We further demonstrated that the introduction of mutated TSC2 into COS-1 cells can generate higher reactive oxygen species (ROS). These results indicate that loss-of-function mutated tuberin can activate Rac1 and thereby increase ROS production. 相似文献
68.
69.
70.
Chromosomal sublocalization and microsatellite DNA polymorphism of human adrenomedullin gene. 总被引:5,自引:0,他引:5
T Ishimitsu K Hosoya K Tsukada J Minami H Ono M Ohrui J Hino K Kangawa H Matsuoka 《Peptides》2001,22(11):1739-1744