全文获取类型
收费全文 | 832篇 |
免费 | 68篇 |
专业分类
900篇 |
出版年
2023年 | 4篇 |
2022年 | 10篇 |
2021年 | 18篇 |
2020年 | 12篇 |
2019年 | 13篇 |
2018年 | 28篇 |
2017年 | 12篇 |
2016年 | 26篇 |
2015年 | 41篇 |
2014年 | 53篇 |
2013年 | 85篇 |
2012年 | 65篇 |
2011年 | 57篇 |
2010年 | 39篇 |
2009年 | 16篇 |
2008年 | 29篇 |
2007年 | 41篇 |
2006年 | 34篇 |
2005年 | 31篇 |
2004年 | 39篇 |
2003年 | 27篇 |
2002年 | 31篇 |
2001年 | 17篇 |
2000年 | 14篇 |
1999年 | 12篇 |
1998年 | 13篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 14篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1979年 | 6篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1967年 | 5篇 |
1925年 | 1篇 |
1921年 | 1篇 |
排序方式: 共有900条查询结果,搜索用时 15 毫秒
11.
12.
Aida M Beis D Heidstra R Willemsen V Blilou I Galinha C Nussaume L Noh YS Amasino R Scheres B 《Cell》2004,119(1):109-120
13.
Srabasti Acharya Brian M. Safaie Piriya Wongkongkathep Magdalena I. Ivanova Aida Attar Frank-Gerrit Kl?rner Thomas Schrader Joseph A. Loo Gal Bitan Lisa J. Lapidus 《The Journal of biological chemistry》2014,289(15):10727-10737
Recent work on α-synuclein has shown that aggregation is controlled kinetically by the rate of reconfiguration of the unstructured chain, such that the faster the reconfiguration, the slower the aggregation. In this work we investigate this relationship by examining α-synuclein in the presence of a small molecular tweezer, CLR01, which binds selectively to Lys side chains. We find strong binding to multiple Lys within the chain as measured by fluorescence and mass-spectrometry and a linear increase in the reconfiguration rate with concentration of the inhibitor. Top-down mass-spectrometric analysis shows that the main binding of CLR01 to α-synuclein occurs at the N-terminal Lys-10/Lys-12. Photo-induced cross-linking of unmodified proteins (PICUP) analysis shows that under the conditions used for the fluorescence analysis, α-synuclein is predominantly monomeric. The results can be successfully modeled using a kinetic scheme in which two aggregation-prone monomers can form an encounter complex that leads to further oligomerization but can also dissociate back to monomers if the reconfiguration rate is sufficiently high. Taken together, the data provide important insights into the preferred binding site of CLR01 on α-synuclein and the mechanism by which the molecular tweezer prevents self-assembly into neurotoxic aggregates by α-synuclein and presumably other amyloidogenic proteins. 相似文献
14.
Hona Hosseinpoor Aida Iraji Najmeh Edraki Somayeh Pirhadi Mahshid Attarroshan Mahsima Khoshneviszadeh Mehdi Khoshneviszadeh 《化学与生物多样性》2020,17(8)
Tyrosinase is a type 3 copper enzyme responsible for skin pigmentation disorders, skin cancer, and enzymatic browning of vegetables and fruits. In the present article, 12 small molecules of 2‐benzylidenehydrazine‐1‐carbothioamide were designed, synthesized and evaluated for their anti‐tyrosinase activities followed by molecular docking and pharmacophore‐based screening. Among synthesized thiosemicarbazone derivatives, one compound, (2E)‐2‐[(4‐nitrophenyl)methylidene]hydrazine‐1‐carbothioamide, is the strongest inhibitor of mushroom tyrosinase with IC50 of 0.05 μM which demonstrated a 128‐fold increase in potency compared to the positive control. Kinetic studies also revealed mix type inhibition by this compound. Docking studies confirmed the complete fitting of the synthesized compounds into the tyrosinase active site. The results underline the potential of 2‐benzylidenehydrazine‐1‐carbothioamides as potent pharmacophore to extend the tyrosinase inhibition in drug discovery. 相似文献
15.
Stuckey DW Clements M Di-Gregorio A Senner CE Le Tissier P Srinivas S Rodriguez TA 《Development (Cambridge, England)》2011,138(8):1521-1530
During development, the growth of the embryo must be coupled to its patterning to ensure correct and timely morphogenesis. In the mouse embryo, migration of the anterior visceral endoderm (AVE) to the prospective anterior establishes the anterior-posterior (A-P) axis. By analysing the distribution of cells in S phase, M phase and G2 from the time just prior to the migration of the AVE until 18 hours after its movement, we show that there is no evidence for differential proliferation along the A-P axis of the mouse embryo. Rather, we have identified that as AVE movements are being initiated, the epiblast proliferates at a much higher rate than the visceral endoderm. We show that these high levels of proliferation in the epiblast are dependent on Nodal signalling and are required for A-P establishment, as blocking cell division in the epiblast inhibits AVE migration. Interestingly, inhibition of migration by blocking proliferation can be rescued by Dkk1. This suggests that the high levels of epiblast proliferation function to move the prospective AVE away from signals that are inhibitory to its migration. The finding that initiation of AVE movements requires a certain level of proliferation in the epiblast provides a mechanism whereby A-P axis development is coordinated with embryonic growth. 相似文献
16.
17.
18.
A new and practical method for the screening of neuraminidase inhibitors (NI) by means of the viral hemagglutination (HA)-dehemagglutination(deHA) reactions was suggested. The best conditions for the HA and deHA reactions were investigated. Existence of strong inhibition activity on the viral deHA has been recognized in the culture filtrates of some strains of actinomycetes. All of these deHA inhibitors showed NI activity that is not specified to the strain of the test viruses. About 0.25 mg/ml of the preparation obtained from the culture filtrate of the strongest actinomycetes, No. 289, inhibited the liberation of neuraminic acid from bovine submaxillary mucin by 80 HA units/ml of influenza A Fukuoka/1/70 (H3N2) virus up to 80%. 相似文献
19.
The α-d-galactosidases of six Streptomyces strains were examined on their inducer susceptibility, substate specificity, and inhibitor susceptibility. In all strains examined, α-d-galactosidase was induced by d-galactose, but neither by d-fucose nor by l-arabinose. α-d-Fucosidase activity was always induced accompanying with α-d-galactosedase activity. β-l-Arabinosidase activity, however, was never observed. These α-d-galactosidases were purified to electrophoretically pure degree by successive ammonium sulfate and ethanol precipitation, and ion exchange and gel filtration chromatography. The purified preparations from six strains were different from each other in their chromatographic behaviors and in some physical properties, but they all showed strong α-d-fucosidase activity as well. The α-d-galactosidase activities were strongly inhibited by d-galactose and l-arabinose, but scarcely by d-fucose. On the other hand, their α-d-fucosidase activities were inhibited by d-fucose as well as by d-galactose and l-arabinose. 相似文献
20.