全文获取类型
收费全文 | 2251篇 |
免费 | 347篇 |
国内免费 | 62篇 |
专业分类
化学 | 2422篇 |
晶体学 | 6篇 |
力学 | 3篇 |
综合类 | 9篇 |
数学 | 7篇 |
物理学 | 213篇 |
出版年
2024年 | 5篇 |
2023年 | 18篇 |
2022年 | 72篇 |
2021年 | 93篇 |
2020年 | 91篇 |
2019年 | 76篇 |
2018年 | 46篇 |
2017年 | 53篇 |
2016年 | 136篇 |
2015年 | 132篇 |
2014年 | 147篇 |
2013年 | 193篇 |
2012年 | 158篇 |
2011年 | 172篇 |
2010年 | 137篇 |
2009年 | 153篇 |
2008年 | 140篇 |
2007年 | 124篇 |
2006年 | 113篇 |
2005年 | 114篇 |
2004年 | 103篇 |
2003年 | 87篇 |
2002年 | 33篇 |
2001年 | 24篇 |
2000年 | 33篇 |
1999年 | 29篇 |
1998年 | 22篇 |
1997年 | 26篇 |
1996年 | 22篇 |
1995年 | 21篇 |
1994年 | 10篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有2660条查询结果,搜索用时 0 毫秒
51.
Glycosyl‐Substituted Dicarboxylates as Detergents for the Extraction,Overstabilization, and Crystallization of Membrane Proteins 下载免费PDF全文
Dr. Kim‐Anh Nguyen Dr. Marine Peuchmaur Sandrine Magnard Dr. Romain Haudecoeur Dr. Cédric Boyère Saravanan Mounien Ikram Benammar Veronica Zampieri Dr. Sébastien Igonet Dr. Vincent Chaptal Dr. Anass Jawhari Prof. Ahcène Boumendjel Dr. Pierre Falson 《Angewandte Chemie (International ed. in English)》2018,57(11):2948-2952
To tackle the problems associated with membrane protein (MP) instability in detergent solutions, we designed a series of glycosyl‐substituted dicarboxylate detergents (DCODs) in which we optimized the polar head to clamp the membrane domain by including, on one side, two carboxyl groups that form salt bridges with basic residues abundant at the membrane–cytoplasm interface of MPs and, on the other side, a sugar to form hydrogen bonds. Upon extraction, the DCODs 8 b , 8 c , and 9 b preserved the ATPase function of BmrA, an ATP‐binding cassette pump, much more efficiently than reference or recently designed detergents. The DCODs 8 a , 8 b , 8 f , 9 a , and 9 b induced thermal shifts of 20 to 29 °C for BmrA and of 13 to 21 °C for the native version of the G‐protein‐coupled adenosine receptor A2AR. Compounds 8 f and 8 g improved the diffraction resolution of BmrA crystals from 6 to 4 Å. DCODs are therefore considered to be promising and powerful tools for the structural biology of MPs. 相似文献
52.
Tunable and Photoswitchable Chemically Induced Dimerization for Chemo‐optogenetic Control of Protein and Organelle Positioning 下载免费PDF全文
Dr. Xi Chen Prof. Dr. Yao‐Wen Wu 《Angewandte Chemie (International ed. in English)》2018,57(23):6796-6799
The spatiotemporal dynamics of proteins and organelles play an important role in controlling diverse cellular processes. Optogenetic tools using photosensitive proteins and chemically induced dimerization (CID), which allow control of protein dimerization, have been used to elucidate the dynamics of biological systems and to dissect the complicated biological regulatory networks. However, the inherent limitations of current optogenetic and CID systems remain a significant challenge for the fine‐tuning of cellular activity at precise times and locations. Herein, we present a novel chemo‐optogenetic approach, photoswitchable chemically induced dimerization (psCID), for controlling cellular function by using blue light in a rapid and reversible manner. Moreover, psCID is tunable; that is, the dimerization and dedimerization degrees can be fine‐tuned by applying different doses of illumination. Using this approach, we control the localization of proteins and positioning of organelles in live cells with high spatial (μm) and temporal (ms) precision. 相似文献
53.
Christina Heroven Victoria Georgi Gaurav K. Ganotra Prof. Paul Brennan Finn Wolfreys Prof. Dr. Rebecca C. Wade Amaury E. Fernández‐Montalván Apirat Chaikuad Prof. Dr. Stefan Knapp 《Angewandte Chemie (International ed. in English)》2018,57(24):7220-7224
Prolonged drug residence times may result in longer‐lasting drug efficacy, improved pharmacodynamic properties, and “kinetic selectivity” over off‐targets with high drug dissociation rates. However, few strategies have been elaborated to rationally modulate drug residence time and thereby to integrate this key property into the drug development process. Herein, we show that the interaction between a halogen moiety on an inhibitor and an aromatic residue in the target protein can significantly increase inhibitor residence time. By using the interaction of the serine/threonine kinase haspin with 5‐iodotubercidin (5‐iTU) derivatives as a model for an archetypal active‐state (type I) kinase–inhibitor binding mode, we demonstrate that inhibitor residence times markedly increase with the size and polarizability of the halogen atom. The halogen–aromatic π interactions in the haspin–inhibitor complexes were characterized by means of kinetic, thermodynamic, and structural measurements along with binding‐energy calculations. 相似文献
54.
55.
Cofactor Biogenesis in Cysteamine Dioxygenase: C−F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine 下载免费PDF全文
Yifan Wang Dr. Wendell P. Griffith Dr. Jiasong Li Dr. Teruaki Koto Dr. Daniel J. Wherritt Elizabeth Fritz Prof. Dr. Aimin Liu 《Angewandte Chemie (International ed. in English)》2018,57(27):8149-8153
Cysteamine dioxygenase (ADO) is a thiol dioxygenase whose study has been stagnated by the ambiguity as to whether or not it possesses an anticipated protein‐derived cofactor. Reported herein is the discovery and elucidation of a Cys‐Tyr cofactor in human ADO, crosslinked between Cys220 and Tyr222 through a thioether (C?S) bond. By genetically incorporating an unnatural amino acid, 3,5‐difluoro‐tyrosine (F2‐Tyr), specifically into Tyr222 of human ADO, an autocatalytic oxidative carbon–fluorine bond activation and fluoride release were identified by mass spectrometry and 19F NMR spectroscopy. These results suggest that the cofactor biogenesis is executed by a powerful oxidant during an autocatalytic process. Unlike that of cysteine dioxygenase, the crosslinking results in a minimal structural change of the protein and it is not detectable by routine low‐resolution techniques. Finally, a new sequence motif, C‐X‐Y‐Y(F), is proposed for identifying the Cys‐Tyr crosslink. 相似文献
56.
采用反相悬浮聚合法合成20%交联度的聚丙烯酰膀(Polyacrylamide,PAM)树脂,经过Mannich反应修饰(nacrylamide:nformaldehyde:ndimethylamine=1:1:1.2)得到高亲水性弱碱性阴离子交换剂氨甲基化聚丙烯酰胺(Aminomcthylated Polyacrylamide,APAM).随着修饰反应时间的增加,得到的APAM的弱碱交换量与蛋白质吸附量增加,在选定的实验条件下,确定Mannich反应时间以1h为宜,所得树脂对牛血清白蛋白吸附量达到433mg/g,过长的反应时间导致树脂结构有一定程度的破坏.树脂对蛋白质的吸附等温线符合Langmuir方程,实际分离牛血清白蛋白和血红蛋白效果较好,柱体积不随洗脱液中盐浓度的增加而变化. 相似文献
57.
Mena ML Moreno-Gordaliza E Moraleja I Cañas B Gómez-Gómez MM 《Journal of chromatography. A》2011,1218(9):1281-1290
In this work a 2D electrophoretic separation procedure able to maintain the integrity of platinum-protein bonds has been developed. The method is based on the use of sequential OFFGEL isoelectric focussing (IEF) and PAGE. A systematic study of the reagents used for PAGE, for OFFGEL-IEF separation, and post-separation treatment of gels (such as enzymatic digestion and sample preparation for MS analysis) was tackled regarding their suitability for the identification of platinum binding proteins using standard proteins incubated with cisplatin. The distribution of platinum in high and low molecular weight fractions (separated by cut-off filters) was determined by ICP-MS, which allows evaluating platinum-protein bond stability under the conditions studied. SDS-PAGE in the absence of β-mercaptoethanol or dithiotreitol preserved the platinum-protein bonds. In addition, neither the influence of the electric field during the electrophoretic separation, nor the processes of fixing, staining and destaining of proteins in the gel did result in the loss of platinum from platinum binding proteins. SDS-PAGE under non-reducing conditions provides separation of platinum-binding proteins in very narrow bands with quantitative recoveries. Different amounts of platinum-bound proteins covering the range 0.3-2.0 μg were separated and mineralised for platinum determination, showing good platinum linearity. Limits of detection for a mixture of five standard proteins incubated with cisplatin were between the range of 2.4 and 13.9 pg of platinum, which were satisfactory for their application to biological samples. Regarding OFFGEL-IEF, a denaturing solution without thiourea and without dithiotreitol is recommended. The suitability of the OFFGEL-IEF for the separation of platinum binding proteins of a kidney cytosol was demonstrated. 相似文献
58.
This review focuses on the progresses and challenges in the preparation of Man3GlcNAc2 (M3) which is the core structure in the N-glycan biological pathway. Representative methods and recent reported findings, especially research advances in chemoenzymatic synthesis, are highlighted. 相似文献
59.
60.
Matthias Meier Dr. Julia Kennedy‐Darling Se Hoon Choi Eric M. Norstrom Dr. Sangram S. Sisodia Prof. Dr. Rustem F. Ismagilov Prof. Dr. 《Angewandte Chemie (International ed. in English)》2009,48(8):1487-1489
Small with control : For miniaturization of protein aggregation experiments the interfacial chemistry must be controlled to avoid protein aggregation caused by interfacial adsorption. Plug‐based microfluidics with defined surface chemistry (see schematic picture) can then be used to perform hundreds of aggregation experiments with volume‐limited samples, such as cerebrospinal fluid from mice.