全文获取类型
收费全文 | 613篇 |
免费 | 52篇 |
出版年
2021年 | 5篇 |
2019年 | 9篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 9篇 |
2015年 | 15篇 |
2014年 | 16篇 |
2013年 | 57篇 |
2012年 | 28篇 |
2011年 | 19篇 |
2010年 | 22篇 |
2009年 | 14篇 |
2008年 | 27篇 |
2007年 | 27篇 |
2006年 | 28篇 |
2005年 | 32篇 |
2004年 | 41篇 |
2003年 | 30篇 |
2002年 | 24篇 |
2001年 | 19篇 |
2000年 | 26篇 |
1999年 | 24篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 20篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 7篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 4篇 |
1969年 | 5篇 |
1968年 | 3篇 |
排序方式: 共有665条查询结果,搜索用时 15 毫秒
101.
Masafumi Komiya Shigehiro Asano Nobuyuki Koike Erina Koga Junetsu Igarashi Shogo Nakatani Yoshiaki Isobe 《Bioorganic & medicinal chemistry》2012,20(23):6840-6847
Based on 2-(4-phenoxybenzoyl)-5-hydroxyindole (2), a novel structural class of CaMKII inhibitors were synthesized and further optimized. The strong acidity of the hydroxyl group and the lipophilic group at the 4 and 6-positions were found to be necessary for strong CaMKII inhibition. Compound 25 was identified as a promising compound with 50-fold more potent inhibitory activity for CaMKII than 2. Compound 25 also showed high selectivity for CaMKII over off-target kinases. 相似文献
102.
par Masanao Matsui Yôichi Nakatani Yasuki Mori et Zirô Nikuni 《Bioscience, biotechnology, and biochemistry》2013,77(9):647-649
The synthesis of 3-hydroxymethyl-4,5,7-trimethoxy-2-naphthoic acid lactone (II) is described. 相似文献
103.
Kota Nakatani Yuta Katano Kenji Kojima Teisuke Takita Rie Yatsunami Satoshi Nakamura 《Bioscience, biotechnology, and biochemistry》2018,82(10):1715-1723
Site saturation mutagenesis library is a recently developed technique, in which any one out of all amino acid residues in a target region is substituted into other 19 amino acid residues. In this study, we used this technique to increase the thermostability of a GH10 xylanase, XynR, from Bacillus sp. strain TAR-1. We hypothesized that the substrate binding region of XynR is flexible, and that the thermostability of XynR will increase if the flexibility of the substrate binding region is decreased without impairing the substrate binding ability. Site saturation mutagenesis libraries of amino acid residues Tyr43–Lys115 and Ala300–Asn325 of XynR were constructed. By screening 480 clones, S92E was selected as the most thermostable one, exhibiting the residual activity of 80% after heat treatment at 80°C for 15 min in the hydrolysis of Remazol Brilliant Blue-xylan. Our results suggest that this strategy is effective for stabilization of GH10 xylanase.
Abbreviations: DNS: 3,5-dinitrosalicylic acid; RBB-xylan: Remazol Brilliant Blue-xylan 相似文献
104.
Adam Heikal Yoshio Nakatani Wanting Jiao Chris Wilson David Rennison Marion R. Weimar Emily J. Parker Margaret A. Brimble Gregory M. Cook 《Bioorganic & medicinal chemistry letters》2018,28(13):2239-2243
Energy generation is a promising area of drug discovery for both bacterial pathogens and parasites. Type II NADH dehydrogenase (NDH-2), a vital respiratory membrane protein, has attracted attention as a target for the development of new antitubercular and antimalarial agents. To date, however, no potent, specific inhibitors have been identified. Here, we performed a site-directed screening technique, tethering-fragment based drug discovery, against wild-type and mutant forms of NDH-2 containing engineered active-site cysteines. Inhibitory fragments displayed IC50 values between 3 and 110?μM against NDH-2 mutants. Possible binding poses were investigated by in silico modelling, providing a basis for optimisation of fragment binding and improved potency against NDH-2. 相似文献
105.
Let's think again about using mammalian temperature‐sensitive mutants to investigate functional molecules—The perspectives from the studies on three mutants showing chromosome instability 下载免费PDF全文
Kimihiko Sugaya 《Journal of cellular biochemistry》2018,119(9):7143-7150
This review evaluates the use of temperature‐sensitive (ts) mutants to investigate functional molecules in mammalian cells. A series of studies were performed in which mammalian cells expressing functional molecules were isolated from ts mutants using complementation by the introduction and expression of the responsible protein tagged with the green fluorescent protein. The results showed that chromosome instability and cell‐cycle arrest were caused by ts defects in the following three molecules: the largest subunit of RNA polymerase II, a protein involved in splicing, and ubiquitin‐activating enzyme. The cells expressing functional protein were then isolated by introducing the responsible gene tagged with the green fluorescent protein to complement the ts phenotype. These cells proved to be useful in analyzing the dynamics of RNA polymerase II in living cells. Analyses of the functional interaction between proteins involved in splicing were also useful in the investigation of ts mutants and their derivatives. In addition, these cells demonstrated the functional localization of ubiquitin‐activating enzyme in the nucleus. Mammalian ts mutants continue to show great potential to aid in understanding the functions of the essential molecules in cells. Therefore, it is highly important that studies on the identification and characterization of the genes responsible for the phenotype of a mutant are carried out. 相似文献
106.
A new limonoid, 7-acetyltrichilin A, has been isolated from the root bark of Trichilia roka and identified as an antifeedant against North American and Japanese pest insects. 相似文献
107.
A kinetic study of saccharopine dehydrogenase reaction 总被引:3,自引:0,他引:3
108.
109.
Notochord cells in ascidian embryos are formed by the inducing action of cells of presumptive endoderm, as well as neighboring presumptive notochord, at the 32-cell stage. Studies of the timing of induction using recombinations of isolated blastomeres have suggested that notochord induction must be initiated before the decompaction of blastomeres at the 32-cell stage and is completed by the 64-cell stage. However, it is not yet clear how the duration of notochord induction is strictly limited. In the present paper, the aim was to determine in detail when the presumptive notochord blastomeres lost their competence to respond, and when the presumptive endoderm blastomeres produced inducing signals for the notochord. Presumptive notochord blastomeres and presumptive endoderm blastomeres were isolated from early 32-cell embryos, and were heterochronously recombined at various stages ranging from the early 32-cell stage to the 64-cell stage. Presumptive notochord blastomeres could respond to inductive signals at the early 32-cell stage, and started to lose their responsiveness at the decompaction stage. By contrast, the presumptive endoderm blastomeres persisted in their inducing capacity even at the 64-cell stage. These observations suggest that the loss of competence in presumptive notochord blastomeres limits the duration of notochord induction in intact ascidian embryos. 相似文献
110.
A Double-Strand Break Repair Component Is Essential for S Phase Completion in Fission Yeast Cell Cycling 下载免费PDF全文
Kimihiko Suto Akihisa Nagata Hiroshi Murakami Hiroto Okayama 《Molecular biology of the cell》1999,10(10):3331-3343
Fission yeast rad22(+), a homologue of budding yeast RAD52, encodes a double-strand break repair component, which is dispensable for proliferation. We, however, have recently obtained a cell division cycle mutant with a temperature-sensitive allele of rad22(+), designated rad22-H6, which resulted from a point mutation in the conserved coding sequence leading to one amino acid alteration. We have subsequently isolated rad22(+) and its novel homologue rti1(+) as multicopy suppressors of this mutant. rti1(+) suppresses all the defects of cells lacking rad22(+). Mating type switch-inactive heterothallic cells lacking either rad22(+) or rti1(+) are viable, but those lacking both genes are inviable and arrest proliferation with a cell division cycle phenotype. At the nonpermissive temperature, a synchronous culture of rad22-H6 cells performs DNA synthesis without delay and arrests with chromosomes seemingly intact and replication completed and with a high level of tyrosine-phosphorylated Cdc2. However, rad22-H6 cells show a typical S phase arrest phenotype if combined with the rad1-1 checkpoint mutation. rad22(+) genetically interacts with rad11(+), which encodes the large subunit of replication protein A. Deletion of rad22(+)/rti1(+) or the presence of rad22-H6 mutation decreases the restriction temperature of rad11-A1 cells by 4-6 degrees C and leads to cell cycle arrest with chromosomes incompletely replicated. Thus, in fission yeast a double-strand break repair component is required for a certain step of chromosome replication unlinked to repair, partly via interacting with replication protein A. 相似文献