全文获取类型
收费全文 | 3771篇 |
免费 | 173篇 |
出版年
2022年 | 26篇 |
2021年 | 54篇 |
2020年 | 31篇 |
2019年 | 37篇 |
2018年 | 69篇 |
2017年 | 40篇 |
2016年 | 78篇 |
2015年 | 126篇 |
2014年 | 139篇 |
2013年 | 206篇 |
2012年 | 253篇 |
2011年 | 242篇 |
2010年 | 150篇 |
2009年 | 134篇 |
2008年 | 223篇 |
2007年 | 234篇 |
2006年 | 214篇 |
2005年 | 181篇 |
2004年 | 230篇 |
2003年 | 197篇 |
2002年 | 163篇 |
2001年 | 62篇 |
2000年 | 69篇 |
1999年 | 68篇 |
1998年 | 35篇 |
1997年 | 22篇 |
1996年 | 26篇 |
1995年 | 30篇 |
1994年 | 32篇 |
1993年 | 20篇 |
1992年 | 65篇 |
1991年 | 43篇 |
1990年 | 30篇 |
1989年 | 33篇 |
1988年 | 48篇 |
1987年 | 40篇 |
1986年 | 22篇 |
1985年 | 25篇 |
1984年 | 22篇 |
1983年 | 28篇 |
1982年 | 11篇 |
1981年 | 15篇 |
1979年 | 24篇 |
1976年 | 11篇 |
1974年 | 14篇 |
1973年 | 12篇 |
1972年 | 12篇 |
1971年 | 10篇 |
1970年 | 13篇 |
1968年 | 13篇 |
排序方式: 共有3944条查询结果,搜索用时 671 毫秒
121.
Takahiro Kodama Hayato Hikita Tsukasa Kawaguchi Yoshinobu Saito Satoshi Tanaka Minoru Shigekawa Satoshi Shimizu Wei Li Takuya Miyagi Tatsuya Kanto Naoki Hiramatsu Tomohide Tatsumi Tetsuo Takehara 《The Journal of biological chemistry》2013,288(42):30009-30018
An intrinsic pathway of apoptosis is regulated by the B-cell lymphoma-2 (Bcl-2) family proteins. We previously reported that a fine rheostatic balance between the anti- and pro-apoptotic multidomain Bcl-2 family proteins controls hepatocyte apoptosis in the healthy liver. The Bcl-2 homology domain 3 (BH3)-only proteins set this rheostatic balance toward apoptosis upon activation in the diseased liver. However, their involvement in healthy Bcl-2 rheostasis remains unknown. In the present study, we focused on two BH3-only proteins, Bim and Bid, and we clarified the Bcl-2 network that governs hepatocyte life and death in the healthy liver. We generated hepatocyte-specific Bcl-xL- or Mcl-1-knock-out mice, with or without disrupting Bim and/or Bid, and we examined hepatocyte apoptosis under physiological conditions. We also examined the effect of both Bid and Bim disruption on the hepatocyte apoptosis caused by the inhibition of Bcl-xL and Mcl-1. Spontaneous hepatocyte apoptosis in Bcl-xL- or Mcl-1-knock-out mice was significantly ameliorated by Bim deletion. The disruption of both Bim and Bid completely prevented hepatocyte apoptosis in Bcl-xL-knock-out mice and weakened massive hepatocyte apoptosis via the additional in vivo knockdown of mcl-1 in these mice. Finally, the hepatocyte apoptosis caused by ABT-737, which is a Bcl-xL/Bcl-2/Bcl-w inhibitor, was completely prevented in Bim/Bid double knock-out mice. The BH3-only proteins Bim and Bid are functionally active but are restrained by the anti-apoptotic Bcl-2 family proteins under physiological conditions. Hepatocyte integrity is maintained by the dynamic and well orchestrated Bcl-2 network in the healthy liver. 相似文献
122.
Variable alteration of regional tissue oxygen pressure in rat hippocampus by acute swimming exercise
One of the events in the brain is an increasing cerebral blood flow during exercise. The tissue oxygen level may be increased because blood flow correlates with tissue oxygen level. However, it is little known whether the tissue oxygen pressure in hippocampal region (Hip-pO2) will be affected by exercise. 相似文献
123.
Koichi Mitsukura Tatsuya Kuramoto Toyokazu Yoshida Norihiro Kimoto Hiroaki Yamamoto Toru Nagasawa 《Applied microbiology and biotechnology》2013,97(18):8079-8086
A NADPH-dependent (S)-imine reductase (SIR) was purified to be homogeneous from the cell-free extract of Streptomyces sp. GF3546. SIR appeared to be a homodimer protein with subunits of 30.5 kDa based on SDS-polyacrylamide gel electrophoresis and HPLC gel filtration. It also catalyzed the (S)-enantioselective reduction of not only 2-methyl-1-pyrroline (2-MPN) but also 1-methyl-3,4-dihydroisoquinoline and 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline. Specific activities for their imines were 130, 44, and 2.6 nmol?min?1?mg?1, and their optical purities were 92.7 % ee, 96.4 % ee, and >99 % ee, respectively. Using a NADPH-regenerating system, 10 mM 2-MPN was converted to amine with 100 % conversion and 92 % ee after 24 h. The amino acid sequence analysis revealed that SIR showed about 60 % identity to 6-phosphogluconate dehydrogenase. However, it showed only 37 % identity with Streptomyces sp. GF3587 (R)-imine reductase. Expression of SIR in Escherichia coli was achieved, and specific activity of the cell-free extract was about two times higher than that of the cell-free extract of Streptomyces sp. GF3546. 相似文献
124.
125.
Tatsuya Kawamoto Yoshifumi Kobayashi Hidenori Nakajima Yukiko Yamagishi 《Biochemical and biophysical research communications》2013
Vascular network formation is a key therapeutic event in regenerative medicine because it is essential for mitigating or ameliorating ischemic conditions implicated in various diseases and repair of tissues and organs. In this study, we induced human induced pluripotent stem cells (hiPSCs) to differentiate into heterogeneous cell populations which have abilities to form vascular vessel-like structures by recapitulating the embryonic process of vasculogenesis in vitro. These cell populations, named cardiovascular blast populations (CBPs) in this report, primarily consisted of CD31+ and CD90+ cells. 相似文献
126.
Takeshi Fujii Masataka G. Suzuki Susumu Katsuma Katsuhiko Ito Yu Rong Shogo Matsumoto Tetsu Ando Yukio Ishikawa 《Biochemical and biophysical research communications》2013
Female Ascotis selenaria (Geometridae) moths use 3,4-epoxy-(Z,Z)-6,9-nonadecadiene, which is synthesized from linolenic acid, as the main component of their sex pheromone. While the use of dietary linolenic or linoleic fatty acid derivatives as sex pheromone components has been observed in moth species belonging to a few families including Geometridae, the majority of moths use derivatives of a common saturated fatty acid, palmitic acid, as their sex pheromone components. We attempted to gain insight into the differentiation of pheromone biosynthetic pathways in geometrids by analyzing the desaturase genes expressed in the pheromone gland of A. selenaria. We demonstrated that a Δ11-desaturase-like gene (Asdesat1) was specifically expressed in the pheromone gland of A. selenaria in spite of the absence of a desaturation step in the pheromone biosynthetic pathway in this species. Further analysis revealed that the presumed transmembrane domains were degenerated in Asdesat1. Phylogenetic analysis demonstrated that Asdesat1 anciently diverged from the lineage of Δ11-desaturases, which are currently widely used in the biosynthesis of sex pheromones by moths. These results suggest that an ancestral Δ11-desaturase became dysfunctional in A. selenaria after a shift in pheromone biosynthetic pathways. 相似文献
127.
Keiichi Konoki Tatsuya Onoda Sachie Furumochi Yuko Cho Mari Yotsu-Yamashita Takeshi Yasumoto 《Bioorganic & medicinal chemistry letters》2013,23(21):5833-5835
The binding between [24-3H]okadaic acid (OA) and a recombinant OA binding protein OABP2.1 was examined using various OA analog, including methyl okadaate, norokadanone, 7-deoxy OA, and 14,15-dihydro OA, 7-O-palmitoyl DTX1, to investigate the structure activity relationship. Among them, 7-O-palmitoyl DTX1, which is one of the diarrhetic shellfish poisoning (DSP) toxins identified in shellfish, displayed an IC50 for [24-3H]OA binding at 51 ± 6.3 nM (Mean ± SD). In addition, a synthetic compound, N-pyrenylmethyl okadamide, exhibited its IC50 at 10 ± 2.9 nM (Mean ± SD). These results suggested that the recombinant OABP2.1 and the N-pyrenylmethyl okadamide might be core substances in a novel assay for the DSP toxins. 相似文献
128.
129.
Tomoyoshi Hosokawa Kunio Ando Gakuzo Tamura 《Bioscience, biotechnology, and biochemistry》2013,77(11):2865-2869
γ-Aminobutyric acid (GABA), a hypotensive compound, and alanine accumulated in tea leaves under anaerobic conditions. Since the 15N in 15N-glutamic acid was well incorporated in GABA and alanine during anaerobic incubation, glutamic acid seemed to be a source of nitrogen for the increased GABA and alanine. GOT and GPT were the predominant amino acid transaminases in tea leaves. Although glutamate decarboxylase and GPT seemed to be important for GABA and alanine accumulation, the activities of these enzymes did not increase under anaerobic conditions. Glutamate decarboxylase, which formed GABA from glutamate, was purified 52.4-fold. This enzyme, with an optimum pH at 5.8, was activated by pyridoxal phosphate and used only l-glutamic acid as a substrate. 相似文献
130.