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11.
Conformation of a synthetic antigenic peptide from HIV-1 p24 protein induced by ionic micelles 总被引:1,自引:0,他引:1
Campana PT Beltramini LM Costa-Filho AJ Tonarelli G Lottersberger J Bianconi ML 《Biophysical chemistry》2005,113(2):175-182
We studied the interaction of the peptide AAMQMLKETINEEAAEWDRVHPVHAGPIA from the HIV-1 p24 protein in the presence of SDS (anionic) and CTABr (cationic) micelles at pH 7.0 by circular dichroism, fluorescence, and electron spin resonance (ESR). The micelles induced secondary structure as well as a blue shift in the tryptophan fluorescence emission, indicating an interaction between the peptide and the micelles. However, different contents of secondary structure elements were found when the peptide interacts with SDS or CTABr micelles. Steady-state anisotropy indicates a constraint on the rotational mobility of the tryptophan residue of the peptide upon interaction with micelles. ESR studies pointed to different locations for the peptide in either micelle. Our results suggested that at least part of the peptide might be located at the hydrophobic core of the CTABr micelles, probably at the C-terminal region, while it is more inserted into the SDS micelles. 相似文献
12.
Carneiro FA Lapido-Loureiro PA Cordo SM Stauffer F Weissmüller G Bianconi ML Juliano MA Juliano L Bisch PM Da Poian AT Poian AT 《European biophysics journal : EBJ》2006,35(2):145-154
The entry of enveloped animal viruses into their host cells always depends on membrane fusion triggered by conformational
changes in viral envelope glycoproteins. Vesicular stomatitis virus (VSV) infection is mediated by virus spike glycoprotein
G, which induces membrane fusion between the viral envelope and the endosomal membrane at the acidic environment of this compartment.
In this work, we evaluated VSV interactions with membranes of different phospholipid compositions, at neutral and acidic pH,
using atomic force microscopy (AFM) operating in the force spectroscopy mode, isothermal calorimetry (ITC) and molecular dynamics
simulation. We found that the binding forces differed dramatically depending on the membrane phospholipid composition, revealing
a high specificity of G protein binding to membranes containing phosphatidylserine (PS). In a previous work, we showed that
the sequence corresponding amino acid 164 of VSV G protein was as efficient as the virus in catalyzing membrane fusion at
pH 6.0. Here, we used this sequence to explore VSV–PS interaction using ITC. We found that peptide binding to membranes was
exothermic, suggesting the participation of electrostatic interactions. Peptide–membrane interaction at pH 7.5 was shown to
be specific to PS and dependent on the presence of His residues in the fusion peptide. The application of the simplified continuum
Gouy–Chapman theory to our system predicted a pH of 5.0 at membrane surface, suggesting that the His residues should be protonated
when located close to the membrane. Molecular dynamics simulations suggested that the peptide interacts with the lipid bilayer
through its N-terminal residues, especially Val145 and His148.
Fabiana A.Carneiro and Pedro A. Lapido-Loureiro contributed equally to this work
An erratum to this article can be found at 相似文献
13.
Bianconi F Baldelli E Ludovini V Crinò L Flacco A Valigi P 《Biotechnology advances》2012,30(1):142-153
In this paper we propose a Systems Biology approach to understand the molecular biology of the Epidermal Growth Factor Receptor (EGFR, also known as ErbB1/HER1) and type 1 Insulin-like Growth Factor (IGF1R) pathways in non-small cell lung cancer (NSCLC). This approach, combined with Translational Oncology methodologies, is used to address the experimental evidence of a close relationship among EGFR and IGF1R protein expression, by immunohistochemistry (IHC) and gene amplification, by in situ hybridization (FISH) and the corresponding ability to develop a more aggressive behavior. We develop a detailed in silico model, based on ordinary differential equations, of the pathways and study the dynamic implications of receptor alterations on the time behavior of the MAPK cascade down to ERK, which in turn governs proliferation and cell migration. In addition, an extensive sensitivity analysis of the proposed model is carried out and a simplified model is proposed which allows us to infer a similar relationship among EGFR and IGF1R activities and disease outcome. 相似文献
14.
Antonio Bianconi Gabriele Ciasca Alexander Tenenbaum Anna Battisti Gaetano Campi 《Journal of biological physics》2012,38(1):169-179
We report the variation with temperature of the ensemble distribution of conformations spanned by the tau protein in its dynamical
states measured by small-angle X-ray scattering (SAXS) using synchrotron radiation. The SAXS data show a clear temperature
variation of the distribution of occupied protein conformations from 293 to 318 K. More conformations with a smaller radius
of gyration are occupied at higher temperature. The protein–solvent interactions are shown by computer simulation to be essential
for controlling the dynamics of protein conformations, providing evidence for the key role of water solvent in the protein
dynamics, as proposed by Giorgio Careri. 相似文献
15.
Fozza C Zoledzieska M Pitzalis M Simula MP Galleu A Contini S Bonfigli S Cucca F Longinotti M 《Immunogenetics》2012,64(2):153-154
Among the different T-cell receptor (TCR) BV20S1 polymorphisms, nucleotide substitution at position 524 results in the introduction
of a stop codon, whose potential functional relevance is still unknown. We have recently showed in Sardinian subjects the
most elevated allele frequency ever reported worldwide for this “null allele” (0.44). As this variant generates a gap in the
TCR repertoire, this preliminary finding prompted us to further analyze the role of this polymorphism in the susceptibility
to type 1 diabetes (T1D) and multiple sclerosis (MS), which are extremely common in this population. With this aim, we evaluated
the influence of the TCRBV20S1 polymorphism by assessing it with the transmission disequilibirum test (TDT) in 652 T1D and
616 MS families, without detecting any significant difference. We conclude that the high frequency of this null allele in
Sardinia is not directly related to the high incidence of these autoimmune diseases observed in this founder population. 相似文献
16.
Matesanz F González-Pérez A Lucas M Sanna S Gayán J Urcelay E Zara I Pitzalis M Cavanillas ML Arroyo R Zoledziewska M Marrosu M Fernández O Leyva L Alcina A Fedetz M Moreno-Rey C Velasco J Real LM Ruiz-Peña JL Cucca F Ruiz A Izquierdo G 《PloS one》2012,7(5):e36140
Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS. 相似文献
17.
Villani M Subathra M Im YB Choi Y Signorelli P Del Poeta M Luberto C 《The Biochemical journal》2008,414(1):31-41
SMS [SM (sphingomyelin) synthase] is a class of enzymes that produces SM by transferring a phosphocholine moiety on to ceramide. PC (phosphatidylcholine) is believed to be the phosphocholine donor of the reaction with consequent production of DAG (diacylglycerol), an important bioactive lipid. In the present study, by modulating SMS1 and SMS2 expression, the role of these enzymes on the elusive regulation of DAG was investigated. Because we found that modulation of SMS1 or SMS2 did not affect total levels of endogenous DAG in resting cells, whereas they produce DAG in vitro, the possibility that SMSs could modulate subcellular pools of DAG, once acute activation of the enzymes is triggered, was investigated. Stimulation of SM synthesis was induced by either treatment with short-chain ceramide analogues or by increasing endogenous ceramide at the plasma membrane, and a fluorescently labelled conventional C1 domain [from PKC (protein kinase C)] enhanced in its DAG binding activity was used to probe subcellular pools of DAG in the cell. With this approach, we found, using confocal microscopy and subcellular fractionation, that modulation of SMS1 and, to a lesser extent, SMS2 affected the formation of DAG at the Golgi apparatus. Similarly, down-regulation of SMS1 and SMS2 reduced the localization of the DAG-binding protein PKD (protein kinase D) to the Golgi. These results provide direct evidence that both enzymes are capable of regulating the formation of DAG in cells, that this pool of DAG is biologically active, and for the first time directly implicate SMS1 and SMS2 as regulators of DAG-binding proteins in the Golgi apparatus. 相似文献
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