全文获取类型
收费全文 | 1020篇 |
免费 | 56篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 7篇 |
2022年 | 14篇 |
2021年 | 27篇 |
2020年 | 20篇 |
2019年 | 29篇 |
2018年 | 29篇 |
2017年 | 32篇 |
2016年 | 36篇 |
2015年 | 56篇 |
2014年 | 52篇 |
2013年 | 79篇 |
2012年 | 87篇 |
2011年 | 83篇 |
2010年 | 53篇 |
2009年 | 45篇 |
2008年 | 65篇 |
2007年 | 56篇 |
2006年 | 50篇 |
2005年 | 40篇 |
2004年 | 43篇 |
2003年 | 40篇 |
2002年 | 34篇 |
2001年 | 17篇 |
2000年 | 16篇 |
1999年 | 13篇 |
1998年 | 8篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1978年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有1077条查询结果,搜索用时 46 毫秒
81.
82.
83.
84.
An integrative approach combining ion mobility mass spectrometry,X-ray crystallography,and nuclear magnetic resonance spectroscopy to study the conformational dynamics of α1-antitrypsin upon ligand binding
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Mun Peak Nyon Tanya Prentice Jemma Day John Kirkpatrick Ganesh N Sivalingam Geraldine Levy Imran Haq James A Irving David A Lomas John Christodoulou Bibek Gooptu Konstantinos Thalassinos 《Protein science : a publication of the Protein Society》2015,24(8):1301-1312
Native mass spectrometry (MS) methods permit the study of multiple protein species within solution equilibria, whereas ion mobility (IM)-MS can report on conformational behavior of specific states. We used IM-MS to study a conformationally labile protein (α1-antitrypsin) that undergoes pathological polymerization in the context of point mutations. The folded, native state of the Z-variant remains highly polymerogenic in physiological conditions despite only minor thermodynamic destabilization relative to the wild-type variant. Various data implicate kinetic instability (conformational lability within a native state ensemble) as the basis of Z α1-antitrypsin polymerogenicity. We show the ability of IM-MS to track such disease-relevant conformational behavior in detail by studying the effects of peptide binding on α1-antitrypsin conformation and dynamics. IM-MS is, therefore, an ideal platform for the screening of compounds that result in therapeutically beneficial kinetic stabilization of native α1-antitrypsin. Our findings are confirmed with high-resolution X-ray crystallographic and nuclear magnetic resonance spectroscopic studies of the same event, which together dissect structural changes from dynamic effects caused by peptide binding at a residue-specific level. IM-MS methods, therefore, have great potential for further study of biologically relevant thermodynamic and kinetic instability of proteins and provide rapid and multidimensional characterization of ligand interactions of therapeutic interest.PDB Code(s): 4PYW 相似文献
85.
Hemantkumar Chavan Feng Li Robert Tessman Kristen Mickey Kenneth Dorko Timothy Schmitt Sean Kumer Sumedha Gunewardena Nilesh Gaikwad Partha Krishnamurthy 《The Journal of biological chemistry》2015,290(12):7871-7886
Although endogenous mechanisms that negatively regulate cytochrome P450 (P450) monooxygenases in response to physiological and pathophysiological signals are not well understood, they are thought to result from alterations in the level of endogenous metabolites, involved in maintaining homeostasis. Here we show that homeostatic changes in hepatic metabolite profile in Abcb6 (mitochondrial ATP-binding cassette transporter B6) deficiency results in suppression of a specific subset of hepatic P450 activity. Abcb6 null mice are more susceptible to pentobarbital-induced sleep and zoxazolamine-induced paralysis, secondary to decreased expression and activity of Cyp3a11 and Cyp2b10. The knock-out mice also show decrease in both basal and xeno-inducible expression and activity of a subset of hepatic P450s that appear to be related to changes in hepatic metabolite profile. These data, together with the observation that liver extracts from Abcb6-deficient mice suppress P450 expression in human primary hepatocytes, suggest that this mouse model may provide an opportunity to understand the physiological signals and the mechanisms involved in negative regulation of P450s. 相似文献
86.
87.
A three dimensional (3D) gold (Au) nanodendrite network porous structure constructed by a simple electrochemical synthetic method has been presented, and its utility for sensitive electrochemical measurement was demonstrated in this study. The 3D nanodendrite network porous structure was constructed on a platinum surface through electrodeposition of Au under the presence of hydrogen bubbles generated from the same surface. Iodide, used as a co-reagent, played an important role in the construction of the nanodendrite network by preventing continual growth of Au into larger agglomerates as well as inhibiting coalescence of neighboring nanodendrites. An electrochemical sensor incorporating the structure was built and used to detect As(III) in ultra low concentration range. For the purpose of comparison, bare gold and gold nanoparticle-incorporated electrodes were also prepared. With the use of 3D nanodendrite network porous structure, a much more sensitive detection of As(III) was possible due to its large surface area. 相似文献
88.
Introduction – The two iridoid glycosides kutkoside and picroside‐I are the active hepatoprotective principles of Picrorhiza kurroa Royle ex Benth (Scrophulariaceae), commonly known as Kutki. Quantitation of these phytoconstituents is important for the routine quality control of Kutki extract. Objective – To develop and validate a simple, precise and rapid thin‐layer chromatography (TLC) method for the simultaneous quantitation of kutkoside and picroside‐I in Kutki extract. Methodology – The analysis was performed on a TLC precoated silica gel 60 F254 plate with ethyl acetate:methanol:glacial acetic acid:formic acid (25:5:1:1, v/v/v/v) as mobile phase. Densitometric evaluation of kutkoside and picroside‐I was carried out at 265 nm and the mobile phase showed good resolution with Rf values 0.42 ± 0.03 and 0.61 ± 0.03 for kutkoside and picroside‐I, respectively. The method was validated in terms of specificity, linearity, accuracy and precision. Results – The content of kutkoside and picroside‐I was found to be 2.18 and 1.90%, respectively, and was comparable with those obtained by HPLC. The linearity was found to be in the range of 80–480 ng/spot for both kutkoside and picroside‐I. The average recovery values were found to be 96.5 and 96.0% for kutkoside and picroside‐I, respectively. Conclusion – The developed method was found to be relatively simple, precise and reproducible for the simultaneous quantitation of kutkoside and picroside‐I. The method does not employ any derivatisation procedure and can be used as a quality control tool for the routine analysis of commercial Kutki extracts. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
89.
90.
Nagarapu L Mateti J Gaikwad HK Bantu R Sheeba Rani M Prameela Subhashini NJ 《Bioorganic & medicinal chemistry letters》2011,21(14):4138-4140
A new series of 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives were synthesized and investigated their anti-inflammatory activities using carrageenan-induced rat paw edema model in vivo. All the synthesized compounds were found to be potent anti-inflammatory agents. 相似文献