全文获取类型
收费全文 | 97篇 |
免费 | 5篇 |
出版年
2021年 | 1篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 1篇 |
2015年 | 2篇 |
2014年 | 2篇 |
2013年 | 5篇 |
2012年 | 5篇 |
2011年 | 2篇 |
2010年 | 2篇 |
2009年 | 2篇 |
2008年 | 3篇 |
2007年 | 9篇 |
2006年 | 6篇 |
2005年 | 2篇 |
2004年 | 1篇 |
2003年 | 5篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1985年 | 1篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有102条查询结果,搜索用时 15 毫秒
51.
Cywin CL Dahmann G Prokopowicz AS Young ER Magolda RL Cardozo MG Cogan DA Disalvo D Ginn JD Kashem MA Wolak JP Homon CA Farrell TM Grbic H Hu H Kaplita PV Liu LH Spero DM Jeanfavre DD O'Shea KM White DM Woska JR Brown ML 《Bioorganic & medicinal chemistry letters》2007,17(1):225-230
An uHTS campaign was performed to identify selective inhibitors of PKC-theta. Initial triaging of the hit set based on selectivity and historical analysis led to the identification of 2,4-diamino-5-nitropyrimidines as potent and selective PKC-theta inhibitors. A homology model and initial SAR is presented demonstrating that a 2-arylalkylamino substituent in conjunction with suitable 4-diamino substituent are essential for achieving selectivity over many kinases. Additional hit to lead profiling is presented on selected compounds. 相似文献
52.
The purpose of this paper is to demonstrate that the interaction of an aqueous soluble enzyme with lipid membranes is influenced by the lipid composition of the interphase. The results show that the interaction of an aqueous soluble protease, Rennet from Mucor miehei, depends on the exposure of the carbonyl and phosphate groups at the membrane interphase. The changes produced by the protease on the surface pressure of monolayers of dimyristoylphosphatidylcholine (DMPC); dioleoylphosphatidylcholine (DOPC); diphytanoylphosphatidylcholine (DPhPC); dipalmitoylphosphatidylcholine (DPPC); di-O-tetradecylphosphatidyl-choline [D(ether)PC]; dimyristoylphosphatidylethanolamine (DMPE); di-O-tetradecyl-phosphatidylethanolamine [D(ether)PE] were measured at different initial surface pressures. The meaning of the DeltaPi vs. Pi curves was interpreted in the light of the concept of interphase given by Defay and Prigogine [R. Defay, I. Prigogine, Surface Tension and Adsorption, John Wiley & Sons, New York, 1966, pp. 273-277] considering the interphase as a bidimensional solution of polar head groups. With this approach, and based on reported evidences that carbonyls and phosphates are the main hydration sites of the lipid membranes, it is suggested that the mechanism of interaction of aqueous soluble protein involves water beyond the hydration shell. At high surface pressure, only water strongly bound to carbonyl and phosphate groups is present and the interaction is not occurring. In contrast, at low surface pressures, the protease-membrane interaction is a function of acyl chain for different polar groups. This is interpreted, as a consequence of the changes in the interfacial tension produced by the displacement of water confined between the hydrated head groups. 相似文献
53.
Cross validation (CV) was used to analyze the effects of different environments and different genotypic samples on estimates of the proportion of genotypic variance explained by QTL (p). Testcrosses of 344 F(3) maize lines grown in four environments were evaluated for a number of agronomic traits. In each of 200 replicated CV runs, this data set was subdivided into an estimation set (ES) and various test sets (TS). ES were used to map QTL and estimate p for each run (p(ES)) and its median (p(ES)) across all runs. The bias of these estimates was assessed by comparison with the median (p(TS.ES)) obtained from TS. We also used two independent validation samples derived from the same cross for further comparison. The median p(ES) showed a large upward bias compared to p(TS.ES). Environmental sampling generally had a smaller effect on the bias of p(ES) than genotypic sampling or both factors simultaneously. In independent validation, p(TS.ES) was on average only 50% of p(ES). A wide range among p(ES) reflected a large sampling error of these estimates. QTL frequency distributions and comparison of estimated QTL effects indicated a low precision of QTL localization and an upward bias in the absolute values of estimated QTL effects from ES. CV with data from three QTL studies reported in the literature yielded similar results as those obtained with maize testcrosses. We therefore recommend CV for obtaining asymptotically unbiased estimates of p and consequently a realistic assessment of the prospects of MAS. 相似文献
54.
55.
Federico M Lauro Matthew Z DeMaere Sheree Yau Mark V Brown Charmaine Ng David Wilkins Mark J Raftery John AE Gibson Cynthia Andrews-Pfannkoch Matthew Lewis Jeffrey M Hoffman Torsten Thomas Ricardo Cavicchioli 《The ISME journal》2011,5(5):879-895
In nature, the complexity and structure of microbial communities varies widely, ranging from a few species to thousands of species, and from highly structured to highly unstructured communities. Here, we describe the identity and functional capacity of microbial populations within distinct layers of a pristine, marine-derived, meromictic (stratified) lake (Ace Lake) in Antarctica. Nine million open reading frames were analyzed, representing microbial samples taken from six depths of the lake size fractionated on sequential 3.0, 0.8 and 0.1 μm filters, and including metaproteome data from matching 0.1 μm filters. We determine how the interactions of members of this highly structured and moderately complex community define the biogeochemical fluxes throughout the entire lake. Our view is that the health of this delicate ecosystem is dictated by the effects of the polar light cycle on the dominant role of green sulfur bacteria in primary production and nutrient cycling, and the influence of viruses/phage and phage resistance on the cooperation between members of the microbial community right throughout the lake. To test our assertions, and develop a framework applicable to other microbially driven ecosystems, we developed a mathematical model that describes how cooperation within a microbial system is impacted by periodic fluctuations in environmental parameters on key populations of microorganisms. Our study reveals a mutualistic structure within the microbial community throughout the lake that has arisen as the result of mechanistic interactions between the physico-chemical parameters and the selection of individual members of the community. By exhaustively describing and modelling interactions in Ace Lake, we have developed an approach that may be applicable to learning how environmental perturbations affect the microbial dynamics in more complex aquatic systems. 相似文献
56.
57.
Maher M. Fadel Faten R. Abdel Ghaffar Shimaa K. Zwain Hany M. Ibrahim Eman AE. badr 《Biochemistry and Biophysics Reports》2021
ObjectiveThis study aimed to evaluate the serum level of netrin and soluble vascular cell adhesion molecule 1 (VCAM-I) in patients with type IΙ diabetes mellitus (T2DM) and evaluate the association of their levels with the development of a diabetic complication.Patients and methodsThis study was carried out on type II diabetic patients with and without complications and healthy individuals served as controls. All subjects were submitted to the estimation of serum lipid profile, serum creatinine, urinary albumin/creatinine ratio (ACR), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), visceral adiposity index (VAI), atherogenic index of plasma (AIP), lipid accumulation product (LAP) and detection of serum level of netrin1 and VCAM1.ResultsDiabetic patients with complications had significantly higher serum levels of creatinine, ACR, cholesterol, Triglyceride, low-density lipoprotein, netrin1, and VCAM1 than diabetic patients without complications. Likewise, the level of VAI and LAP as markers of excessive body fat were significantly higher in diabetic patients with complications than diabetic patients without complications. The netrin1 and VCAM1 were a significant discriminator of T2DM renal complications with a sensitivity of 96%, 90%, and specificity of 82.7%, 91.3% respectively.ConclusionIt can be concluded that serum netrin1 and VCAM1 correlated significantly with markers of excessive body fat, a renal complication in the patient with type 2 diabetes mellitus. 相似文献
58.
AE Clarke S Bernatsky KH Costenbader MB Urowitz DD Gladman PR Fortin M Petri S Manzi DA Isenberg A Rahman D Wallace C Gordon C Peschken MA Dooley EM Ginzler C Aranow SM Edworthy O Nived S Jacobsen G Ruiz-Irastorza E Yelin SG Barr L Criswell G Sturfelt L Dreyer I Blanco L Gottesman CH Feldman R Ramsey-Goldman 《Arthritis research & therapy》2012,14(Z3):A16
59.
Frías MA Winik B Franzoni MB Levstein PR Nicastro A Gennaro AM Diaz SB Disalvo EA 《Biochimica et biophysica acta》2008,1778(5):1259-1266
Arbutin is known to suppress melanin production in murine B16 melanoma cells and inhibit phospholipase action. This encourages the possibility to stabilize it in lipid aggregates for its administration in medical applications. Thus, it was of interest to demonstrate that monomyristoylphosphatidylcholine (14:0 lysoPC) and arbutin may form association complexes. This was studied by Electron Microscopy (EM), 31P Nuclear Magnetic Resonance (31P NMR), Electronic Paramagnetic Resonance (EPR) and Fourier Transform Infrared Spectroscopy (FTIR). EM images show the formation of particles of c.a. 6 nm in diameter. For a 1:1 lysoPC-arbutin molar ratio 31P NMR shows a spectrum with a shoulder that resembles the axially symmetric spectrum characteristic of vesicles. The addition of La3+ ions to the arbutin-lysoPC complex allows one to distinguish two phosphorous populations. These results suggest that arbutin-lysoPC forms vesicles with bilayers stabilized in an interdigitated array. FTIR spectroscopy shows that arbutin interacts with the hydrated population of the carbonyl groups and with the phosphates through the formation of hydrogen bonds. It is interpreted that hydrophobic interactions among the phenol group of arbutin and the acyl chain of lysoPC are responsible for the decrease in acyl chain mobility observed at the 5th C level by EPR. A model proposing the formation of interdigitated bilayers of arbutin-lysoPC could explain the experimental results. 相似文献
60.
The proteolytic activity of an aspartyl protease of Mucor miehei was correlated with the adsorption of the protease to lipid vesicles. It was observed that the presence of phosphatidylethanolamines (PE's) in the membrane increased the enzyme activity in a 20% in the gel phase and 10% in the fluid phase. The effects of protease on the surface pressure of monolayers composed by dioleoylphosphatidylcholine (DOPC), dimyristoylphosphatidylcholine (DMPC), dimyristoyl phosphatidylethanolamine (DMPE) were measured at constant temperature as a function of the surface pressure. At low surface pressures, the major changes were induced by protease on DOPC and DMPC monolayers. However, the effect were much lower when the monolayer was composed by DMPE. The low hydration and strong head-head interaction between the phosphates and the amine groups of adjacent PE's would result in an area per molecule much lower in PE than in phosphatidylcholine (PC) in concordance with the lower penetration in PE. Protease adsorption on PE membranes increases the proteolytic activity in which condition is less susceptible to inhibition by pepstatin. However, PC's do not alter the enzyme activity being the action of inhibitor unaffected. 相似文献