全文获取类型
收费全文 | 107篇 |
免费 | 9篇 |
国内免费 | 4篇 |
出版年
2022年 | 1篇 |
2019年 | 1篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 11篇 |
2013年 | 6篇 |
2012年 | 7篇 |
2011年 | 4篇 |
2010年 | 9篇 |
2009年 | 7篇 |
2008年 | 6篇 |
2007年 | 2篇 |
2006年 | 2篇 |
2005年 | 5篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1983年 | 4篇 |
1978年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有120条查询结果,搜索用时 111 毫秒
51.
Alemayehu A Gorfe Philippe Ferrara Amedeo Caflisch Daniel N Marti Hans Rudolf Bosshard Ilian Jelesarov 《Proteins》2002,46(1):41-60
The use of conformational ensembles provided by nuclear magnetic resonance (NMR) experiments or generated by molecular dynamics (MD) simulations has been regarded as a useful approach to account for protein motions in the context of pK(a) calculations, yet the idea has been tested occasionally. This is the first report of systematic comparison of pK(a) estimates computed from long multiple MD simulations and NMR ensembles. As model systems, a synthetic leucine zipper, the naturally occurring coiled coil GCN4, and barnase were used. A variety of conformational averaging and titration curve-averaging techniques, or combination thereof, was adopted and/or modified to investigate the effect of extensive global conformational sampling on the accuracy of pK(a) calculations. Clustering of coordinates is proposed as an approach to reduce the vast diversity of MD ensembles to a few structures representative of the average electrostatic properties of the system in solution. Remarkable improvement of the accuracy of pK(a) predictions was achieved by the use of multiple MD simulations. By using multiple trajectories the absolute error in pK(a) predictions for the model leucine zipper was reduced to as low as approximately 0.25 pK(a) units. The validity, advantages, and limitations of explicit conformational sampling by MD, compared with the use of an average structure and a high internal protein dielectric value as means to improve the accuracy of pK(a) calculations, are discussed. 相似文献
52.
53.
Schmidt K Marx A de Graaf AA Wiechert W Sahm H Nielsen J Villadsen J 《Biotechnology and bioengineering》1998,58(2-3):254-257
Conventional metabolic flux analysis uses the information gained from determination of measurable fluxes and a steady-state assumption for intracellular metabolites to calculate the metabolic fluxes in a given metabolic network. The determination of intracellular fluxes depends heavily on the correctness of the assumed stoichiometry including the presence of all reactions with a noticeable impact on the model metabolite balances. Determination of fluxes in complex metabolic networks often requires the inclusion of NADH and NADPH balances, which are subject to controversial debate. Transhydrogenation reactions that transfer reduction equivalents from NADH to NADPH or vice versa can usually not be included in the stoichiometric model, because they result in singularities in the stoichiometric matrix. However, it is the NADPH balance that, to a large extent, determines the calculated flux through the pentose phosphate pathway. Hence, wrong assumptions on the presence or activity of transhydrogenation reactions will result in wrong estimations of the intracellular flux distribution. Using 13C tracer experiments and NMR analysis, flux analysis can be performed on the basis of only well established stoichiometric equations and measurements of the labeling state of intracellular metabolites. Neither NADH/NADPH balancing nor assumptions on energy yields need to be included to determine the intracellular fluxes. Because metabolite balancing methods and the use of 13C labeling measurements are two different approaches to the determination of intracellular fluxes, both methods can be used to verify each other or to discuss the origin and significance of deviations in the results. Flux analysis based entirely on metabolite balancing and flux analysis, including labeling information, have been performed independently for a wild-type strain of Aspergillus oryzae producing alpha-amylase. Two different nitrogen sources, NH4+ and NO3-, have been used to investigate the influence of the NADPH requirements on the intracellular flux distribution. The two different approaches to the calculation of fluxes are compared and deviations in the results are discussed. Copyright 1998 John Wiley & Sons, Inc. 相似文献
54.
55.
56.
57.
André M Siqueira Lucas I Coutinho Rafael L Gurgel Willian CS Su Luiz M Carvalho Silvana G Benzecry Aline CC Alencar Márcia AA Alexandre Maria Gra?as C Alecrim Marcus VG Lacerda 《Memórias do Instituto Oswaldo Cruz》2014,109(5):540-545
Plasmodium vivax is the most widespread parasite causing malaria, being
especially prevalent in the Americas and Southeast Asia. Children are one of the
most affected populations, especially in highly endemic areas. However, there are
few studies evaluating the therapeutic response of infants with vivax malaria.
This study retrospectively evaluated the parasitaemia clearance in children
diagnosed with vivax malaria during the first five days of exclusive treatment
with chloroquine (CQ). Infants aged less than six months old had a significantly
slower parasitaemia clearance time compared to the group of infants and children
between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon
test; p = 0.004). The impaired clearance of parasitaemia in younger children with
vivax malaria is shown for the first time in Latin America. It is speculated that
CQ pharmacokinetics in young children with vivax malaria is distinct, but this
specific population may also allow the detection of CQ-resistant parasites during
follow-up, due to the lack of previous immunity. 相似文献
58.
Uwe Thissen Suzan Wopereis Sjoerd AA van den Berg Ivana Bobeldijk Robert Kleemann Teake Kooistra Ko Willems van Dijk Ben van Ommen Age K Smilde 《BMC bioinformatics》2009,10(1):52
Background
In the fields of life sciences, so-called designed studies are used for studying complex biological systems. The data derived from these studies comply with a study design aimed at generating relevant information while diminishing unwanted variation (noise). Knowledge about the study design can be used to decompose the total data into data blocks that are associated with specific effects. Subsequent statistical analysis can be improved by this decomposition if these are applied on selected combinations of effects. 相似文献59.
The XI International Rotifer Symposium was held during 11–18 March, 2006 at the National Autonomous University of Mexico Campus Iztacala located at the North Mexico City (Mexico). These triennial international meetings, first organized in Austria by Late Ruttner-Kolisko in September 1976, are gradually becoming the focal point of discussion and collaboration from rotifer workers across the world. The present XI symposium was attended by 125 participants from 20 nations. During this meeting, different themes of rotifer research from morphology to molecular biology were considered. In addition, there were four invited lectures and four workshops covering different themes of the symposium. During the last 30 years, rotifer research has witnessed gradual shift from the conventional morphological taxonomy to molecular and evolutionary systematics. While the basic rotifer ecological studies continue today, applied areas such as ecotoxicology and aquaculture have taken key roles in the recent meetings. The international rotifer meetings provide ample opportunities not only for exchange of ideas and recent research, but also for material and in establishing inter-personal relationships. Over the last 30 years, the number of participants attending the rotifer meetings has increased. 相似文献
60.
Prakash P Sayyed-Ahmad A Zhou Y Volk DE Gorenstein DG Dial E Lichtenberger LM Gorfe AA 《Biochimica et biophysica acta》2012,1818(12):3040-3047
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat chronic pain and inflammation. However, prolonged use of NSAIDs has been known to result in Gastrointestinal (GI) ulceration/bleeding, with a bile-mediated mechanism underlying their toxicity to the lower gut. Bile acids (BAs) and phosphatidylcholines (PCs), the major components of bile, form mixed micelles to reduce the membrane disruptive actions of monomeric BAs and simple BA micelles. NSAIDs are suspected to alter the BA/PC balance in the bile, but the molecular interactions of NSAID-BA or NSAID-BA-PC remain undetermined. In this work, we used a series of all-atom molecular dynamics simulations of cholic acid (CA), ibuprofen (IBU) and dodecylphosphocholine (DPC) mixtures to study the spontaneous aggregation of CA and IBU as well as their adsorption on a DPC micelle. We found that the size of CA-IBU mixed micelles varies with their molar ratio in a non-linear manner, and that micelles of different sizes adopt similar shapes but differ in composition and internal interactions. These observations are supported by NMR chemical shift changes, NMR ROESY crosspeaks between IBU and CA, and dynamic light scattering experiments. Smaller CA-IBU aggregates were formed in the presence of a DPC micelle due to the segregation of CA and IBU away from each other by the DPC micelle. While the larger CA-IBU aggregates arising from higher IBU concentrations might be responsible for NSAID-induced intestinal toxicity, the absence of larger CA-IBU aggregates in the presence of DPC micelles may explain the observed attenuation of NSAID toxicity by PCs. 相似文献