全文获取类型
收费全文 | 3188篇 |
免费 | 178篇 |
国内免费 | 2篇 |
出版年
2023年 | 9篇 |
2022年 | 11篇 |
2021年 | 56篇 |
2020年 | 28篇 |
2019年 | 47篇 |
2018年 | 73篇 |
2017年 | 68篇 |
2016年 | 86篇 |
2015年 | 131篇 |
2014年 | 166篇 |
2013年 | 217篇 |
2012年 | 226篇 |
2011年 | 252篇 |
2010年 | 143篇 |
2009年 | 135篇 |
2008年 | 197篇 |
2007年 | 187篇 |
2006年 | 184篇 |
2005年 | 170篇 |
2004年 | 184篇 |
2003年 | 182篇 |
2002年 | 147篇 |
2001年 | 36篇 |
2000年 | 33篇 |
1999年 | 29篇 |
1998年 | 33篇 |
1997年 | 29篇 |
1996年 | 27篇 |
1995年 | 25篇 |
1994年 | 13篇 |
1993年 | 22篇 |
1992年 | 22篇 |
1991年 | 18篇 |
1990年 | 21篇 |
1989年 | 16篇 |
1988年 | 11篇 |
1987年 | 12篇 |
1986年 | 15篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 14篇 |
1982年 | 12篇 |
1980年 | 5篇 |
1979年 | 9篇 |
1977年 | 5篇 |
1975年 | 4篇 |
1974年 | 6篇 |
1973年 | 4篇 |
1971年 | 4篇 |
1967年 | 4篇 |
排序方式: 共有3368条查询结果,搜索用时 78 毫秒
81.
Kenichiro Kinouchi Atsuhiro Ichihara Motoaki Sano Ge-Hong Sun-Wada Yoh Wada Hiroki Ochi Toru Fukuda Kanako Bokuda Hideaki Kurosawa Naohiro Yoshida Shu Takeda Keiichi Fukuda Hiroshi Itoh 《PloS one》2013,8(11)
The ATPase 6 accessory protein 2 (ATP6AP2)/(pro)renin receptor (PRR) is essential for the biogenesis of active vacuolar H+-ATPase (V-ATPase). Genetic deletion of ATP6AP2/PRR causes V-ATPase dysfunction and compromises vesicular acidification. Here, we characterized the domains of ATP6AP2/PRR involved in active V-ATPase biogenesis. Three forms of ATP6AP2/PRR were found intracellularly: full-length protein and the N- and C-terminal fragments of furin cleavage products, with the N-terminal fragment secreted extracellularly. Genetic deletion of ATP6AP2/PRR did not affect the protein stability of V-ATPase subunits. The extracellular domain (ECD) and transmembrane domain (TM) of ATP6AP2/PRR were indispensable for the biogenesis of active V-ATPase. A deletion mutant of ATP6AP2/PRR, which lacks exon 4-encoded amino acids inside the ECD (Δ4M) and causes X-linked mental retardation Hedera type (MRXSH) and X-linked parkinsonism with spasticity (XPDS) in humans, was defective as a V-ATPase-associated protein. Prorenin had no effect on the biogenesis of active V-ATPase. The cleavage of ATP6AP2/PRR by furin seemed also dispensable for the biogenesis of active V-ATPase. We conclude that the N-terminal ECD of ATP6AP2/PRR, which is also involved in binding to prorenin or renin, is required for the biogenesis of active V-ATPase. The V-ATPase assembly occurs prior to its delivery to the trans-Golgi network and hence shedding of ATP6AP2/PRR would not affect the biogenesis of active V-ATPase. 相似文献
82.
Ryunosuke Ohkawa Hann Low Nigora Mukhamedova Ying Fu Shao-Jui Lai Mai Sasaoka Ayuko Hara Azusa Yamazaki Takahiro Kameda Yuna Horiuchi Peter J. Meikle Gerard Pernes Graeme Lancaster Michael Ditiatkovski Paul Nestel Boris Vaisman Denis Sviridov Andrew Murphy Alan T. Remaley Dmitri Sviridov Minoru Tozuka 《Journal of lipid research》2020,61(12):1577
Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1+/+ and Abca1−/− mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain. 相似文献
83.
Yanagisawa Takahiro Ishii Masakazu Takahashi Manami Fujishima Kei Nishimura Masahiro 《Molecular biology reports》2020,47(9):6841-6854
Molecular Biology Reports - LL-37, the only member of the cathelicidin family of cationic antimicrobial peptides in humans has been shown to exhibit a wide variety of biological actions in addition... 相似文献
84.
Nishiyama Misa Nakamichi Noritaka Yoshimura Tomoyuki Masuo Yusuke Komori Tomoe Ishimoto Takahiro Matsuo Jun-ichi Kato Yukio 《Neurochemical research》2020,45(11):2664-2678
Neurochemical Research - Understanding of the underlying mechanism of epilepsy is desired since some patients fail to control their seizures. The carnitine/organic cation transporter OCTN1/SLC22A4... 相似文献
85.
86.
Akiko Kita Asako Kishimoto Takahiro Shimosaka Hiroya Tomita Yuusuke Yokooji Tadayuki Imanaka Haruyuki Atomi Kunio Miki 《Proteins》2020,88(5):718-724
The coenzyme A biosynthesis pathways in most archaea involve two unique enzymes, pantoate kinase and phosphopantothenate synthetase, to convert pantoate to 4′-phosphopantothenate. Here, we report the first crystal structure of pantoate kinase from the hyperthermophilic archaeon, Thermococcus kodakarensis and its complex with ATP and a magnesium ion. The electron density for the adenosine moiety of ATP was very weak, which most likely relates to its broad nucleotide specificity. Based on the structure of the active site that contains a glycerol molecule, the pantoate binding site and the roles of the highly conserved residues are suggested. 相似文献
87.
88.
Yudai Nagata Jae Man Lee Hiroaki Mon Shigeo Imanishi Sun Mee Hong Shoji Komatsu Yuji Oshima Takahiro Kusakabe 《Biotechnology letters》2013,35(7):1009-1016
Glycoproteins have various biological functions including enzymatic activity, protein stability and others. Due to the presence of paucimannosidic N-linked glycans, recombinant proteins from an insect cell expression system may not be suitable for therapeutic use. Because baculovirus expression systems (BESs) are used to produce recombinant proteins, it is of interest to modify the endogenous N-glycosylation pathway in insects to mimic that of mammals. Using a soaking RNAi sensitive cell line, BmN4-SID1, has enabled us to suppress Bombyx mori FDL (BmFDL), an N-linked glycan-specific β-N-acetylglucosaminidase. Western blotting and MALDI-TOF MS demonstrated that the BmFDL depletion almost completely converted the paucimannosidic structures of the recombinant proteins produced by BES into a complex-type structure. This highly efficient, simple and low-cost method can be used for mass production of secretion proteins with complex-type N-linked glycans. 相似文献
89.
Koji Ando Shigetomo Fukuhara Takahiro Moriya Yutaro Obara Norimichi Nakahata Naoki Mochizuki 《The Journal of cell biology》2013,202(6):901-916
Reorganization of the actin cytoskeleton is responsible for dynamic regulation of endothelial cell (EC) barrier function. Circumferential actin bundles (CAB) promote formation of linear adherens junctions (AJs) and tightening of EC junctions, whereas formation of radial stress fibers (RSF) connected to punctate AJs occurs during junction remodeling. The small GTPase Rap1 induces CAB formation to potentiate EC junctions; however, the mechanism underlying Rap1-induced CAB formation remains unknown. Here, we show that myotonic dystrophy kinase–related CDC42-binding kinase (MRCK)-mediated activation of non-muscle myosin II (NM-II) at cell–cell contacts is essential for Rap1-induced CAB formation. Our data suggest that Rap1 induces FGD5-dependent Cdc42 activation at cell–cell junctions to locally activate the NM-II through MRCK, thereby inducing CAB formation. We further reveal that Rap1 suppresses the NM-II activity stimulated by the Rho–ROCK pathway, leading to dissolution of RSF. These findings imply that Rap1 potentiates EC junctions by spatially controlling NM-II activity through activation of the Cdc42–MRCK pathway and suppression of the Rho–ROCK pathway. 相似文献
90.
Takahiro Seki Lijie Gong Aislinn J. Williams Norio Sakai Sokol V. Todi Henry L. Paulson 《The Journal of biological chemistry》2013,288(24):17145-17155
The functional diversity of deubiquitinating enzymes (DUBs) is not well understood. The MJD family of DUBs consists of four cysteine proteases that share a catalytic “Josephin” domain. The family is named after the DUB ATXN3, which causes the neurodegenerative disease Machado-Joseph disease. The two closely related Josephin domain-containing (JosD) proteins 1 and 2 consist of little more than the Josephin domain. To gain insight into the properties of Josephin domains, we investigated JosD1 and JosD2. JosD1 and JosD2 were found to differ fundamentally in many respects. In vitro, only JosD2 can cleave ubiquitin chains. In contrast, JosD1 cleaves ubiquitin chains only after it is monoubiquitinated, a form of posttranslational-dependent regulation shared with ATXN3. A significant fraction of JosD1 is monoubiquitinated in diverse mouse tissues. In cell-based studies, JosD2 localizes to the cytoplasm whereas JosD1 preferentially localizes to the plasma membrane, particularly when ubiquitinated. The membrane occupancy by JosD1 suggests that it could participate in membrane-dependent events such as cell motility and endocytosis. Indeed, time-lapse imaging revealed that JosD1 enhances membrane dynamics and cell motility. JosD1 also influences endocytosis in cultured cells by increasing the uptake of endocytic markers of macropinocytosis while decreasing those for clathrin- and caveolae-mediated endocytosis. Our results establish that two closely related DUBs differ markedly in activity and function and that JosD1, a membrane-associated DUB whose activity is regulated by ubiquitination, helps regulate membrane dynamics, cell motility, and endocytosis. 相似文献