全文获取类型
收费全文 | 470篇 |
免费 | 33篇 |
国内免费 | 26篇 |
出版年
2024年 | 2篇 |
2023年 | 9篇 |
2022年 | 21篇 |
2021年 | 23篇 |
2020年 | 18篇 |
2019年 | 13篇 |
2018年 | 23篇 |
2017年 | 12篇 |
2016年 | 18篇 |
2015年 | 21篇 |
2014年 | 36篇 |
2013年 | 45篇 |
2012年 | 25篇 |
2011年 | 32篇 |
2010年 | 17篇 |
2009年 | 20篇 |
2008年 | 26篇 |
2007年 | 33篇 |
2006年 | 26篇 |
2005年 | 23篇 |
2004年 | 11篇 |
2003年 | 15篇 |
2002年 | 10篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
排序方式: 共有529条查询结果,搜索用时 281 毫秒
121.
合成生物学专注于可重复利用模块和元件的工程化设计,并在生物系统中表现出良好的行为和功能。在无细胞蛋白表达系统中,核糖核酸调节子作为即时检测中的重要传感元件,通过靶标分子的诱导使其自身结构发生变化,进而调控下游基因的表达。系统介绍不同类型的核糖核酸调节子及其作用原理,包括一代核糖核酸调节子、toehold开关、功能拓展的核糖核酸调节子和核糖开关。详细阐明构建核糖核酸调节子的设计-测试-分析过程:计算机辅助设计、基因表达测试和结构功能化分析。汇总基于核糖核酸调节子的体外即时检测应用,重点总结toehold开关介导的病原菌核酸检测和核糖开关参与的小分子检测。讨论当前无细胞即时检测的特点、挑战和发展趋势,为开发新型核糖核酸调节子和即时检测工具提供思路和参考。 相似文献
122.
123.
Kar3 kinesins are microtubule (MT) minus‐end‐directed motors with pleiotropic functions in mitotic spindle formation and nuclear movement in budding and fission yeasts. A Kar3‐like kinesin is also expressed by the filamentous fungus Ashbya gossypi, which exhibits different nuclear movement challenges from its yeast relatives. Presented here is a 2.35 Å crystal structure and enzymatic analysis of the AgKar3 motor domain (AgKar3MD). Compared to the previously published Saccharomyces cerevisiae Kar3MD structure (ScKar3MD), AgKar3MD displays differences in the conformation of some of its nucleotide‐binding motifs and peripheral elements. Unlike ScKar3MD, the salt bridge between Switch I and Switch II in AgKar3MD is broken. Most of the Switch I, and the adjoining region of helix α3, are also disordered instead of bending into the active site cleft as is observed in ScKar3MD. These aspects of AgKar3MD are highly reminiscent of the ScKar3 R598A mutant that disrupts the Switch I–Switch II salt bridge and impairs MT‐stimulated ATPase activity of the motor. Subtle differences in the disposition of secondary structure elements in the small lobe (β1a, β1b, and β1c) at the edge of the MD are also apparent even though it contains approximately the same number of residues as ScKar3. These differences may reflect the unique enzymatic properties we measured for this motor, which include a lower MT‐stimulated ATPase rate relative to ScKar3, or they could relate to its interactions with different regulatory companion proteins than its budding yeast counterpart. Proteins 2011;. © 2011 Wiley Periodicals, Inc. 相似文献
124.
Cornelius Klöck Chaitan Khosla 《Protein science : a publication of the Protein Society》2012,21(12):1781-1791
Mammalian transglutaminases catalyze post‐translational modifications of glutamine residues on proteins and peptides through transamidation or deamidation reactions. Their catalytic mechanism resembles that of cysteine proteases. In virtually every case, their enzymatic activity is modulated by elaborate strategies including controlled gene expression, allostery, covalent modification, and proteolysis. In this review, we focus on our current knowledge of post‐translational regulation of transglutaminase activity by physiological as well as synthetic allosteric agents. Our discussion will primarily focus on transglutaminase 2, but will also compare and contrast its regulation with Factor XIIIa as well as transglutaminases 1 and 3. Potential structure–function relationships of known mutations in human transglutaminases are analyzed. 相似文献
125.
A study of the conformational spaces of the chiral proton pump inhibitor (PPI) drug omeprazole by semiempirical, ab-initio, and DFT methods is described. In addition to the chiral center at the sulfinyl sulfur atom, the chiral axis at the pyridine ring (due to the hindered rotation of the 4-methoxy substituents) was considered. The results were analyzed in terms of the 5-methoxy and 6-methoxy tautomers and the two pairs of enantiomers (R,P)/(S,M) and (R,M)/(S,P). Five torsion angles were systematically explored: the backbone rotations defined by D1 (N3-C2-S10-O11), D2 (C2-S10-C12-C13), and D3 (S10-C12-C13-N14) and two methoxy rotations defined by D4 (C6-C5-O8-C9) and D5 (C16-C17-O19-C20). Significant energy differences were revealed between the 5- and 6-methoxy tautomers, the extended and folded conformations, and the (S,M) and (S,P) diastereomers. The "extended M" conformation of the 6-methoxy tautomer of (S)-omeprazole was found to be the most stable conformer. 相似文献
126.
A series of new mononuclear polypyridyl ruthenium(II) complexes containing two imidazole groups have been synthesized and characterized by 1H NMR, ES-MS, FAB-MS, IR spectra and elemental analysis. Their electrochemistry and spectroscopic properties including UV-Vis absorption, steady-state and time-resolved emission have been studied using both experimental methods and theoretical calculations. These complexes have been found to be sensitive luminescent pH switches, as their absorption and emission spectra respond to the solutions pH disturbances with extraordinary sensitivity, through the protonation and deprotonation of the imidazole groups. DFT calculations have been carried out to reveal the exact protonation and deprotonation route. The ground-state and excited-state ionization constants (pKa and ) of each acid-base equilibrium have also been calculated according to the absorbance and emission data under different pH. 相似文献
127.
128.
129.
130.
The human fungal pathogen Candida albicans changes from a budding yeast form to a polarized hyphal form in response to various external conditions. Dimorphic switching of C. albicans has been implicated in the development of pathogenicity. Morphogenic transformation requires polarized cell growth and rearrangement of the cytoskeleton. We previously showed that myosins play key roles in the conversion from the bud to the hyphal form of C. albicans by inhibiting myosin activities with 2,3-butanedione-2-monoxime (BDM), a general myosin ATPase inhibitor. In this study we investigated the function of MYO2 in C. albicans using deletion mutants. The amino acid sequence of CaMYO2 shows 60% identity and 77% homology with MYO2 and 54% identity and 70% homology with MYO4 of budding yeast Saccharomyces cerevisiae, suggesting that CaMYO2 is the only class V myosin in C. albicans. Cells in which both CaMYO2 alleles were deleted were viable, suggesting that MYO2 is nonessential in C. albicans. The proliferation of CaMYO2delta cells, however, was sharply decreased. In addition, CaMYO2delta cells showed defects in assembly and polarized localization of F-actin as well as an inability to induce germ tube formation and hyphal growth. The deletion of CaMYO2 also disrupted the shape and migration of the nucleus. These results strongly suggest that CaMYO2 is essential for polarized growth and hyphal transition in C. albicans. 相似文献