全文获取类型
收费全文 | 400篇 |
免费 | 15篇 |
国内免费 | 2篇 |
出版年
2022年 | 4篇 |
2021年 | 14篇 |
2020年 | 4篇 |
2018年 | 4篇 |
2017年 | 6篇 |
2016年 | 10篇 |
2015年 | 15篇 |
2014年 | 16篇 |
2013年 | 30篇 |
2012年 | 22篇 |
2011年 | 27篇 |
2010年 | 11篇 |
2009年 | 15篇 |
2008年 | 16篇 |
2007年 | 21篇 |
2006年 | 13篇 |
2005年 | 25篇 |
2004年 | 16篇 |
2003年 | 19篇 |
2002年 | 12篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1996年 | 4篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1964年 | 2篇 |
排序方式: 共有417条查询结果,搜索用时 312 毫秒
31.
Synthesis and NMR solution structure of an alpha-helical hairpin stapled with two disulfide bridges
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)
Barthe P Rochette S Vita C Roumestand C 《Protein science : a publication of the Protein Society》2000,9(5):942-955
Helical coiled-coils and bundles are some of the most common structural motifs found in proteins. Design and synthesis of alpha-helical motifs may provide interesting scaffolds that can be useful as host structures to display functional sites, thus allowing the engineering of novel functional miniproteins. We have synthesized a 38-amino acid peptide, alpha2p8, encompassing the alpha-helical hairpin present in the structure of p8MTCP1, as an alpha-helical scaffold particularly promising for its stability and permissiveness of sequence mutations. The three-dimensional structure of this peptide has been solved using homonuclear two-dimensional NMR techniques at 600 MHz. After sequence specific assignment, a total of 285 distance and 29 dihedral restraints were collected. The solution structure of alpha2p8 is presented as a set of 30 DIANA structures, further refined by restrained molecular dynamics, using simulated annealing protocol with the AMBER force field. The RMSD values for the backbone and all heavy atoms are 0.65+/-0.25 and 1.51+/-0.21 A, respectively. Excised from its protein context, the alpha-hairpin keeps its native structure: an alpha-helical coiled-coil, similar to that found in superhelical structures, with two helices spanning residues 4-16 and 25-36, and linked by a short loop. This motif is stabilized by two interhelical disulfide bridges and several hydrophobic interactions at the helix interface, leaving most of its solvent-exposed surface available for mutation. This alpha-helical hairpin, easily amenable to synthetic chemistry and biological expression system, may represent a stable and versatile scaffold to display new functional sites and peptide libraries. 相似文献
32.
High affinity RGD-binding sites at the plasma membrane of
Arabidopsis thaliana
links the cell wall 总被引:6,自引:0,他引:6
Hervé Canut Antoine Carrasco Jean-Philippe Galaud Catherine Cassan Huguette Bouyssou Natalio Vita Pascual Ferrara Rafael Pont-Lezica 《The Plant journal : for cell and molecular biology》1998,16(1):63-71
The heptapeptide Tyr-Gly- Arg-Gly-Asp- Ser-Pro containing the sequence Arg-Gly-Asp (RGD – the essential structure recognised by animal cells in substrate adhesion molecules) was tested on epidermal cells of onion and cultured cells of Arabidopsis upon plasmolysis. Dramatic changes were observed on both types of cells following treatment: on onion cells, Hechtian strands linking the cell wall to the membrane were lost, while Arabidopsis cells changed from concave to convex plasmolysis. A control heptapeptide Tyr-Gly-Asp-Gly-Arg-Ser-Pro had no effect on the shape of plasmolysed cells. Protoplasts isolated from Arabidopsis cells agglutinate in the presence of ProNectinF, a genetically engineered protein of 72 kDa containing 13 RGD sequences: several protoplasts may adhere to a single molecule of ProNectinF. The addition of the RGD-heptapeptide disrupted the adhesion between the protoplasts. Purified plasma membrane from Arabidopsis cells exhibits specific binding sites for the iodinated RGD-heptapeptide. The binding is saturable, reversible, and two types of high affinity sites (Kd1 1 nM, and Kd2 40 nM) can be discerned. Competitive inhibition by several structurally related peptides and proteins noted the specific requirement for the RGD sequence. Thus, the RGD-binding activity of Arabidopsis fulfils the adhesion features of integrins, i.e. peptide specificity, subcellular location, and involvement in plasma membrane-cell wall attachments. 相似文献
33.
34.
35.
Francesco M. Carpi Silvia Vincenzetti Daniela Micozzi Alberto Vita Valerio Napolioni 《Molecular biology reports》2010,37(7):3363-3368
Cytidine deaminase (CDA) is a pyrimidine salvage pathway enzyme that catalyzes the hydrolytic deamination of cytidine and deoxycytidine to their
corresponding uracil nucleosides. CDA also catalyzes the inactivation of some chemotherapeutic nucleoside analogues such as cytosine arabinoside and gemcitabine.
CDA 79A > C (K27Q, rs2072671) and 208G > A (A70T, rs60369023) were found to be associated either with clinical outcomes as well as with pharmacokinetics and toxicity of drugs administered
to different subsets of patients. In this paper we reported two PCR-based methods for CDA 79A > C (K27Q) and 208G > A (A70T) genotyping and tested their feasibility using DNA extracted from whole blood as well as
from buccal swabs. The aim of this study was also to assess the distribution of genotypic variants in a central Italy population.
The allele frequencies were 56.3% (K*) and 43.7% (Q*) for K27Q and 100% (A*) and 0% (T*) for A70T. The genotype frequencies
were 32.8% (K*/K*), 46.9% (K*/Q*) and 20.3% (Q*/Q*) for K27Q. The genotype frequencies did not deviate from Hardy–Weinberg
equilibrium. The results were compared with those of other reported populations. They showed marked ethnic group differences. 相似文献
36.
Zahra Najarzadeh Masihuz Zaman Vita Sereikaite Kristian Strmgaard Maria Andreasen Daniel E. Otzen 《The Journal of biological chemistry》2021,297(2)
Phenol-soluble modulins (PSMs), such as α-PSMs, β-PSMs, and δ-toxin, are virulence peptides secreted by different Staphylococcus aureus strains. PSMs are able to form amyloid fibrils, which may strengthen the biofilm matrix that promotes bacterial colonization of and extended growth on surfaces (e.g., cell tissue) and increases antibiotic resistance. Many components contribute to biofilm formation, including the human-produced highly sulfated glycosaminoglycan heparin. Although heparin promotes S. aureus infection, the molecular basis for this is unclear. Given that heparin is known to induce fibrillation of a wide range of proteins, we hypothesized that heparin aids bacterial colonization by promoting PSM fibrillation. Here, we address this hypothesis using a combination of thioflavin T-fluorescence kinetic studies, CD, FTIR, electron microscopy, and peptide microarrays to investigate the mechanism of aggregation, the structure of the fibrils, and identify possible binding regions. We found that heparin accelerates fibrillation of all α-PSMs (except PSMα2) and δ-toxin but inhibits β-PSM fibrillation by blocking nucleation or reducing fibrillation levels. Given that S. aureus secretes higher levels of α-PSM than β-PSM peptides, heparin is therefore likely to promote fibrillation overall. Heparin binding is driven by multiple positively charged lysine residues in α-PSMs and δ-toxins, the removal of which strongly reduced binding affinity. Binding of heparin did not affect the structure of the resulting fibrils, that is, the outcome of the aggregation process. Rather, heparin provided a scaffold to catalyze or inhibit fibrillation. Based on our findings, we speculate that heparin may strengthen the bacterial biofilm and therefore enhance colonization via increased PSM fibrillation. 相似文献
37.
Coccaro E Mraiche F Malo M Vandertol-Vanier H Bullis B Robertson M Fliegel L 《Molecular and cellular biochemistry》2007,302(1-2):145-155
We examined two expression systems for studying the Na+/H+ exchanger in the mammalian myocardium. Mammalian NHE1 with a hemagglutinin (HA) tag and was cloned behind the alpha myosin
heavy chain promoter. Transgenic mice were made with wild type NHE1 protein or with a hyperactive NHE1 protein mutated at
the calmodulin-binding domain. Three lines of transgenic mice were made of each cDNA with expression levels of each type varying
from high to low. Higher levels and activity of the Na+/H+ exchanger were associated with decreased long-term survival of mice, and with dilated or hypertrophic cardiomyopathy. The
exogenous NHE1 protein was present in freshly made cardiomyocytes from transgenic mice, however, expression from the alpha
myosin heavy chain promoter declined rapidly and little exogenous NHE1 was apparent on the fourth day after cardiomyocyte
isolation. To express NHE1 protein in isolated cardiomyocytes, we transferred a mutated form of the protein into an adenoviral
expression system. Infection of neonatal rat cardiomyocytes resulted in robust expression of the exogenous NHE1 protein. The
mutant form of the NHE1 protein could be distinguished from the endogenous Na+/H+ exchanger by its resistance to inhibition by amiloride analogs. Our results suggest that for in vivo studies on intact hearts
and animals, expression in transgenic mice is an appropriate system, however for long-term studies on cardiomyocytes, this
model is inappropriate due to waning expression from the alpha myosin heavy chain promoter. Therefore, infection by adenovirus
is a superior system for long-term studies on cardiomyocytes in culture. 相似文献
38.
Bobba A Atlante A Moro L Calissano P Marra E 《Apoptosis : an international journal on programmed cell death》2007,12(9):1597-1610
The involvement and the role of nitric oxide (NO) as a signaling molecule in the course of neuronal apoptosis, whether unique
or modulated during the progression of the apoptotic program, has been investigated in a cellular system consisting of cerebellar
granule cells (CGCs) where apoptosis can be induced by lowering extracellular potassium. Several parameters involved in NO
signaling pathway, such as NO production, neuronal nitric oxide synthase (nNOS) expression, and cyclic GMP (cGMP) production
were examined in the presence or absence of different inhibitors. We provide evidence that nitric oxide has dual and opposite
effects depending on time after induction of apoptosis. In an early phase, up to 3 h of apoptosis, nitric oxide supports survival
of CGCs through a cGMP-dependent mechanism. After 3 h, nNOS expression and activity decreased resulting in shut down of NO
and cGMP production. Residual NO then contributes to the apoptotic process by reacting with rising superoxide anions leading
to peroxynitrite production and protein inactivation. We conclude that whilst NO over-production protects neurons from death
in the early phase of neuronal damage, its subsequent reduction may contribute to neuronal degeneration and ultimate cell
death. 相似文献
39.
40.