全文获取类型
收费全文 | 158篇 |
免费 | 23篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 12篇 |
2014年 | 7篇 |
2013年 | 6篇 |
2012年 | 10篇 |
2011年 | 9篇 |
2010年 | 4篇 |
2009年 | 9篇 |
2008年 | 11篇 |
2007年 | 11篇 |
2006年 | 8篇 |
2005年 | 8篇 |
2004年 | 5篇 |
2003年 | 7篇 |
2002年 | 5篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有181条查询结果,搜索用时 15 毫秒
121.
Yi Zhang Melanie Berghaus Sean Klein Kelly Jenkins Siwen Zhang Scott A. McCallum Joel E. Morgan Roland Winter Doug Barrick Catherine A. Royer 《Journal of molecular biology》2018,430(9):1336-1349
Many repeat proteins contain capping motifs, which serve to shield the hydrophobic core from solvent and maintain structural integrity. While the role of capping motifs in enhancing the stability and structural integrity of repeat proteins is well documented, their contribution to folding cooperativity is not. Here we examined the role of capping motifs in defining the folding cooperativity of the leucine-rich repeat protein, pp32, by monitoring the pressure- and urea-induced unfolding of an N-terminal capping motif (N-cap) deletion mutant, pp32-?N-cap, and a C-terminal capping motif destabilization mutant pp32-Y131F/D146L, using residue-specific NMR and small-angle X-ray scattering. Destabilization of the C-terminal capping motif resulted in higher cooperativity for the unfolding transition compared to wild-type pp32, as these mutations render the stability of the C-terminus similar to that of the rest of the protein. In contrast, deletion of the N-cap led to strong deviation from two-state unfolding. In both urea- and pressure-induced unfolding, residues in repeats 1–3 of pp32-ΔN-cap lost their native structure first, while the C-terminal half was more stable. The residue-specific free energy changes in all regions of pp32-ΔN-cap were larger in urea compared to high pressure, indicating a less cooperative destabilization by pressure. Moreover, in contrast to complete structural disruption of pp32-ΔN-cap at high urea concentration, its pressure unfolded state remained compact. The contrasting effects of the capping motifs on folding cooperativity arise from the differential local stabilities of pp32, whereas the contrasting effects of pressure and urea on the pp32-ΔN-cap variant arise from their distinct mechanisms of action. 相似文献
122.
Immunological similarities between specific chloroplast ribosomal proteins from Chlamydomonas reinhardtii and ribosomal proteins from Escherichia coli 总被引:11,自引:0,他引:11
Polyclonal antibodies were elicited against seven of the 33 different
proteins of the large subunit of the chloroplast ribosome from
Chlamydomonas reinhardtii. Three of these proteins are synthesized in the
chloroplast and four are made in the cytoplasm and imported. In western
blots, six of the seven antisera are monospecific for their respective
large subunit ribosomal proteins, and none of these antisera cross-reacted
with any chloroplast small subunit proteins from C. reinhardtii. Antisera
to the three chloroplast-synthesized ribosomal proteins cross-reacted with
specific Escherichia coli large subunit proteins of comparable charge and
molecular weight. Only one of the four antisera to the chloroplast
ribosomal proteins synthesized in the cytoplasm cross-reacted with an E.
coli large subunit protein. None of the antisera cross-reacted with any E.
coli small subunit proteins. On the assumption of a procaryotic,
endosymbiotic origin for the chloroplast, those chloroplast ribosomal
proteins still synthesized within the organelle appear to have retained
more antigenic sites in common with E. coli ribosomal proteins than have
those which are now the products of cytoplasmic protein synthesis. Antisera
to this cytoplasmically synthesized group of chloroplast ribosomal proteins
did not recognize any antigenic sites among C. reinhardtii cytoplasmic
ribosomal proteins, suggesting that the genes for the cytoplasmically
synthesized chloroplast ribosomal proteins either are not derived from the
cytoplasmic ribosomal protein genes or have evolved to a point where no
antigenic similarities remain.
相似文献
123.
Rossi MS; Barrio E; Latorre A; Quezada-Diaz JE; Hasson E; Moya A; Fontdevila A 《Molecular biology and evolution》1996,13(2):314-323
Both original and colonizer populations of Drosophila buzzatii have been
analyzed for mtDNA restriction polymorphisms. Most of the mtDNA nucleotide
variation in original populations of NW Argentina can be explained by
intrapopulation diversity and only a small fraction can be accounted for by
between-population diversity. Similar results are obtained using either the
estimated number of nucleotide substitutions per site or considering each
restriction site as a locus. Colonizer populations of the Iberian Peninsula
are monomorphic and show only the most common haplotype from the original
populations. Under the infinite island model and assuming that populations
are in equilibrium, fixation indices indicate enough gene flow to explain
why the populations are not structured. Yet, the possibility exists that
populations have not reached an equilibrium after a founder event at the
end of the last Pleistocene glaciation. Tajima's test suggests that
directional selection and/or a recent bottleneck could explain the present
mtDNA differentiation. Considering the significant population structure
found for the chromosomal and some allozyme polymorphisms, the among-
population uniformity for mtDNA variability argues in favor of the
chromosomal and some allozyme polymorphisms being adaptive.
相似文献
124.
Michaël C Fontaine Stuart JE Baird Sylvain Piry Nicolas Ray Krystal A Tolley Sarah Duke Alexei Birkun Jr Marisa Ferreira Thierry Jauniaux Ángela Llavona Bayram Öztürk Ayaka A Öztürk Vincent Ridoux Emer Rogan Marina Sequeira Ursula Siebert Gísli A Vikingsson Jean-Marie Bouquegneau Johan R Michaux 《BMC biology》2007,5(1):1-16
Background
Understanding the role of seascape in shaping genetic and demographic population structure is highly challenging for marine pelagic species such as cetaceans for which there is generally little evidence of what could effectively restrict their dispersal. In the present work, we applied a combination of recent individual-based landscape genetic approaches to investigate the population genetic structure of a highly mobile extensive range cetacean, the harbour porpoise in the eastern North Atlantic, with regards to oceanographic characteristics that could constrain its dispersal.Results
Analyses of 10 microsatellite loci for 752 individuals revealed that most of the sampled range in the eastern North Atlantic behaves as a 'continuous' population that widely extends over thousands of kilometres with significant isolation by distance (IBD). However, strong barriers to gene flow were detected in the south-eastern part of the range. These barriers coincided with profound changes in environmental characteristics and isolated, on a relatively small scale, porpoises from Iberian waters and on a larger scale porpoises from the Black Sea.Conclusion
The presence of these barriers to gene flow that coincide with profound changes in oceanographic features, together with the spatial variation in IBD strength, provide for the first time strong evidence that physical processes have a major impact on the demographic and genetic structure of a cetacean. This genetic pattern further suggests habitat-related fragmentation of the porpoise range that is likely to intensify with predicted surface ocean warming. 相似文献125.
Background
Riboswitches are noncoding RNA structures that appropriately regulate genes in response to changing cellular conditions. The expression of many proteins involved in fundamental metabolic processes is controlled by riboswitches that sense relevant small molecule ligands. Metabolite-binding riboswitches that recognize adenosylcobalamin (AdoCbl), thiamin pyrophosphate (TPP), lysine, glycine, flavin mononucleotide (FMN), guanine, adenine, glucosamine-6-phosphate (GlcN6P), 7-aminoethyl 7-deazaguanine (preQ1), and S-adenosylmethionine (SAM) have been reported. 相似文献126.
Roth A Winkler WC Regulski EE Lee BW Lim J Jona I Barrick JE Ritwik A Kim JN Welz R Iwata-Reuyl D Breaker RR 《Nature structural & molecular biology》2007,14(4):308-317
A previous bioinformatics-based search for riboswitches yielded several candidate motifs in eubacteria. One of these motifs commonly resides in the 5' untranslated regions of genes involved in the biosynthesis of queuosine (Q), a hypermodified nucleoside occupying the anticodon wobble position of certain transfer RNAs. Here we show that this structured RNA is part of a riboswitch selective for 7-aminomethyl-7-deazaguanine (preQ(1)), an intermediate in queuosine biosynthesis. Compared with other natural metabolite-binding RNAs, the preQ(1) aptamer appears to have a simple structure, consisting of a single stem-loop and a short tail sequence that together are formed from as few as 34 nucleotides. Despite its small size, this aptamer is highly selective for its cognate ligand in vitro and has an affinity for preQ(1) in the low nanomolar range. Relatively compact RNA structures can therefore serve effectively as metabolite receptors to regulate gene expression. 相似文献
127.
Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline 总被引:6,自引:1,他引:5
Weinberg Z Barrick JE Yao Z Roth A Kim JN Gore J Wang JX Lee ER Block KF Sudarsan N Neph S Tompa M Ruzzo WL Breaker RR 《Nucleic acids research》2007,35(14):4809-4819
We applied a computational pipeline based on comparative genomics to bacteria, and identified 22 novel candidate RNA motifs. We predicted six to be riboswitches, which are mRNA elements that regulate gene expression on binding a specific metabolite. In separate studies, we confirmed that two of these are novel riboswitches. Three other riboswitch candidates are upstream of either a putative transporter gene in the order Lactobacillales, citric acid cycle genes in Burkholderiales or molybdenum cofactor biosynthesis genes in several phyla. The remaining riboswitch candidate, the widespread Genes for the Environment, for Membranes and for Motility (GEMM) motif, is associated with genes important for natural competence in Vibrio cholerae and the use of metal ions as electron acceptors in Geobacter sulfurreducens. Among the other motifs, one has a genetic distribution similar to a previously published candidate riboswitch, ykkC/yxkD, but has a different structure. We identified possible non-coding RNAs in five phyla, and several additional cis-regulatory RNAs, including one in ε-proteobacteria (upstream of purD, involved in purine biosynthesis), and one in Cyanobacteria (within an ATP synthase operon). These candidate RNAs add to the growing list of RNA motifs involved in multiple cellular processes, and suggest that many additional RNAs remain to be discovered. 相似文献
128.
Barrick CJ Rojas M Schoonhoven R Smyth SS Threadgill DW 《American journal of physiology. Heart and circulatory physiology》2007,292(5):H2119-H2130
Left ventricular hypertrophy (LVH), a risk factor for cardiovascular morbidity and mortality, is commonly caused by essential hypertension. Three geometric patterns of LVH can be induced by hypertension: concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Clinical studies suggest that different underlying etiologies, genetic modifiers, and risk of mortality are associated with LVH geometric patterns. Since pressure overload-induced LVH can be modeled experimentally using transverse aortic constriction (TAC) and since C57BL/6J (B6) and 129S1/SvImJ (129S1) strains, which have different baseline cardiovascular phenotypes, are commonly used, we conducted serial echocardiographic studies to assess cardiac function up to 8 wk of post-TAC in male B6, 129S1, and B6129F1 (F1) mice. B6 mice had an earlier onset and more pronounced impairment in contractile function, with corresponding left and right ventricular dilatation, fibrosis, change in expression of hypertrophy marker, and increased liver weights at 5 wk of post-TAC. These observations suggest that B6 mice had eccentric hypertrophy with systolic dysfunction and right-sided heart failure. In contrast, we found that 129S1 and F1 mice delayed transition to decompensated heart failure, with 129S1 mice exhibiting preserved systolic function until 8 wk of post-TAC and relatively mild alterations in histology and markers of hypertrophy at 5 wk post-TAC. Consistent with concentric hypertrophy, our results show that these strains manifest different cardiac responses to pressure overload in a time-dependent manner and that genetic susceptibility to initial concentric hypertrophy is dominant to eccentric hypertrophy. These results also imply that genetic background differences can complicate interpretation of TAC studies when using mixed genetic backgrounds. 相似文献
129.
This study focuses on the cytotoxic effects of fumonisin B1 (FB1) on both immortalised and immortalised and subsequently transfected normal human bronchial epithelial (NHBE) cells of human
origin using four bioassays. While the MTT, Neutral Red and hexosaminidase colorimetric assays showed little difference between
the toxic effects on the two related cell lines, the clonogenic assay, measuring cell survival and proliferation, indicated
that FB1 had a more toxic effect on the nontransfected cells. This kind ofin vitro approach using cells which retain many characteristics of normal cell growth and differentiation can go some way to developing
evaluation models for food safety in the case of mycotoxin contamination without resorting totally to whole animal testing.
Nevertheless, one or two cytotoxicity tests may be inadequate for a complete appraisal of toxic potential: rather, as wide
a range of methodologies as feasible should be employed initially before meaningful conclusions may be drawn. 相似文献
130.
WJ Richardson DD van der Voort E Wilson JE Moore Jr. 《Molecular & cellular biomechanics : MCB》2013,10(3):245-265
Non-uniform stress and strain fields are prevalent in many tissues in vivo, and often exacerbated by disease or injury. These mechanical gradients potentially play a role in contributing to pathological conditions, presenting a need for experimental tools to allow investigation of cell behavior within non-uniformly stimulated environments. Herein, we employ two in vitro cell-stretching devices (one previously published; one newly presented) capable of subjecting cells to cyclic, non-uniform stretches upon the surface of either a circular elastomeric membrane or a cylindrical PDMS tube. After 24 hours of cyclic stretch, 10T1/2 cells on both devices showed marked changes in long-axis orientation, with tendencies to align parallel to the direction of minimal deformation. The degree of this response varied depending on location within the stretch gradients. These results demonstrated the feasibility of conducting cell mechanobiology investigations with the two novel devices, while also highlighting the experimental capabilities of non-uniform mechanical environments for these types of studies. Such capabilities include robust data collection for developing mechanobiological dose-response curves, signal threshold identification, and potential spatial targeting for drug delivery. 相似文献