全文获取类型
收费全文 | 317篇 |
免费 | 62篇 |
出版年
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 13篇 |
2015年 | 16篇 |
2014年 | 16篇 |
2013年 | 11篇 |
2012年 | 13篇 |
2011年 | 12篇 |
2010年 | 12篇 |
2009年 | 5篇 |
2008年 | 8篇 |
2007年 | 10篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 4篇 |
2003年 | 13篇 |
2002年 | 10篇 |
2001年 | 12篇 |
2000年 | 19篇 |
1999年 | 18篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 6篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 10篇 |
1987年 | 10篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1974年 | 2篇 |
1973年 | 4篇 |
1971年 | 2篇 |
1965年 | 2篇 |
1934年 | 1篇 |
排序方式: 共有379条查询结果,搜索用时 312 毫秒
41.
42.
Simple neural network models of the Xenopus embryo swimming CPG, based on the one originally developed by Roberts and Tunstall (1990), were used to investigate the role of the voltage-dependent N-methyl-D-aspartate (NMDA) receptor channels, in conjunction with faster non-NMDA components of synaptic excitation, in rhythm generation. The voltage-dependent NMDA current "follows" the membrane potential, leading to a postinhibitory rebound that is more efficient than one without voltage dependency and allows neurons to fire more than one action potential per cycle. Furthermore, the model demonstrated limited rhythmic activity in the absence of synaptic inhibition, supporting the hypothesis that the NMDA channels provide a basic mechanism for rhythmicity. However, the rhythmic properties induced by the NMDA current were observed only when there was moderate activation of the non-NMDA synaptic channels, suggesting a modulatory role for this component. The simulations also show that the voltage dependency of the NMDA conductance, as well as the fast non-NMDA current, stabilizes the alternation pattern versus synchrony. To verify that these effects and their implications on the mechanism of swimming and transition to other types of activity take place in the real preparation, constraints on parameter values have to be specified. A method to estimate synaptic parameters was tested with generated data. It is shown that a global analysis, based on multiple iterations of the optimization process (Foster et al., 1993), gives a better understanding of the parameter subspace describing network activity than a standard fit with a sensitivity analysis for an individual solution. 相似文献
43.
Glossoscolex paulistus extracellular hemoglobin (HbGp) oligomeric dissociation upon interaction with sodium dodecyl sulfate: Isothermal titration calorimetry (ITC) 下载免费PDF全文
Fernanda Rosa Alves Francisco Adriano O. Carvalho José Wilson P. Carvalho Marcel Tabak 《Biopolymers》2014,101(10):1065-1076
Annelid erythrocruorins are respiratory proteins with high cooperativity and low autoxidation rates. The giant extracellular hemoglobin of the earthworm, Glossoscolex paulistus (HbGp), has a molecular mass of 3.6 MDa. In this work, isothermal titration calorimetry (ITC), together with DLS and fluorescence emission have been used to investigate the interaction of SDS with the HbGp in the oxy‐form, at pH 7.0. Our ITC and DLS results show that addition of SDS induces oxy‐HbGp oligomeric dissociation, while a small amount of protein aggregation is observed only by DLS. Moreover, the oligomeric dissociation process is favored at lower protein concentrations. The temperature effect does not influence significantly the interaction of SDS with the hemoglobin, due to the similarities presented by the critical aggregation concentration (cac) and critical micelle concentration (cmc′) for the mixtures. The increase of oxy‐HbGp concentration leads to a slight variation of the cac values for the SDS‐oxy‐HbGp mixture, attributed mainly to the noncooperative electrostatic binding of surfactant to protein. However, the cmc′ values increase considerably, associated to a more cooperative hydrophobic binding. Complementary pyrene fluorescence emission studies show formation of pre‐micellar structures of the mixture already at lower SDS concentrations. This study opens the possibility of the evaluation of the surfactant effect on the hemoglobin stability by ITC, which is made for the first time with this extracellular hemoglobin. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 1065–1076, 2014. 相似文献
44.
Marijn Rutgers Daniël BF Saris Wouter JA Dhert Laura B Creemers 《Arthritis research & therapy》2010,12(3):R114
Introduction
Intraarticular administration of autologous conditioned serum (ACS) recently demonstrated some clinical effectiveness in treatment of osteoarthritis (OA). The current study aims to evaluate the in vitro effects of ACS on cartilage proteoglycan (PG) metabolism, its composition and the effects on synovial fluid (SF) cytokine levels following intraarticular ACS administration. 相似文献45.
Patricia S. Santiago Leonardo M. MoreiraErika V. de Almeida Marcel Tabak 《Biochimica et Biophysica Acta (BBA)/General Subjects》2007
The effects of two ionic surfactants on the oligomeric structure of the giant extracellular hemoglobin of Glossoscolex paulistus (HbGp) in the oxy - form have been studied through the use of several spectroscopic techniques such as electronic optical absorption, fluorescence emission, light scattering, and circular dichroism. The use of anionic sodium dodecyl sulphate (SDS) and cationic cethyltrimethyl ammonium chloride (CTAC) has allowed to differentiate the effects of opposite headgroup charges on the oligomeric structure dissociation and hemoglobin autoxidation. At pH 7.0, both surfactants induce the protein dissociation and a significant oxidation. Spectral changes occur at very low CTAC concentrations suggesting a significant electrostatic contribution to the protein–surfactant interaction. At low protein concentration, 0.08 mg/ml, some light scattering within a narrow CTAC concentration range occurs due to protein–surfactant precipitation. Light scattering experiments showed the dissociation of the oligomeric structure by SDS and CTAC, and the effect of precipitation induced by CTAC. At higher protein concentrations, 3.0 mg/ml, a precipitation was observed due to the intense charge neutralization upon formation of ion pair in the protein–surfactant precipitate. The spectral changes are spread over a much wider SDS concentration range, implying a smaller electrostatic contribution to the protein–surfactant interactions. The observed effects are consistent with the acid isoelectric point (pI) of this class of hemoglobins, which favors the intense interaction of HbGp with the cationic surfactant due to the existence of excess acid anionic residues at the protein surface. Protein secondary structure changes are significant for CTAC at low concentrations while they occur at significantly higher concentrations for SDS. In summary, the cationic surfactant seems to interact more strongly with the protein producing more dramatic spectral changes as compared to the anionic one. This is opposite as observed for several other hemoproteins. The surfactants at low concentrations produce the oligomeric dissociation, which facilitates the iron oxidation, an important factor modulating further oligomeric protein dissociation. 相似文献
46.
Podeszwa B Niedbala H Polanski J Musiol R Tabak D Finster J Serafin K Milczarek M Wietrzyk J Boryczka S Mol W Jampilek J Dohnal J Kalinowski DS Richardson DR 《Bioorganic & medicinal chemistry letters》2007,17(22):6138-6141
The structure-activity relationships of new quinoline based compounds were investigated. Quinoline-5,8-dione and styrylquinoline scaffolds were used for the design of potentially active compounds. The novel analogues had comparable antiproliferative activity to cisplatin when evaluated in a bioassay against the P388 leukemia cell line. However, these compounds appeared far less efficient against SK-N-MC neuroepithelioma cells. Analogues without the 5,8-dione structure but containing the 8-carboxylic acid group were also found to induce antiproliferative activity. Hydrophobicity as measured by HPLC did not correlate with antiproliferative activity. 相似文献
47.
48.
R Gon?alves LA Szmuchrowski LS Prado BP Couto JCQ Machado VO Damasceno JA Lamounier 《Biology of sport / Institute of Sport》2015,32(3):255-260
The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children. 相似文献
49.
David Gendron Anne-Marie Lemay Claudine Tremblay Laetitia JA Lai Anick Langlois émilie Bernatchez Nicolas Flamand Marie-Renée Blanchet Anthony S Don Ynuk Bossé élyse Bissonnette David Marsolais 《Respiratory research》2015,16(1)