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141.
Charles D Criscione Claudia LL Valentim Hirohisa Hirai Philip T LoVerde Timothy JC Anderson 《Genome biology》2009,10(6):R71-13
Background
Schistosoma mansoni is a blood fluke that infects approximately 90 million people. The complete life cycle of this parasite can be maintained in the laboratory, making this one of the few experimentally tractable human helminth infections, and a rich literature reveals heritable variation in important biomedical traits such as virulence, host-specificity, transmission and drug resistance. However, there is a current lack of tools needed to study S. mansoni's molecular, quantitative, and population genetics. Our goal was to construct a genetic linkage map for S. mansoni, and thus provide a new resource that will help stimulate research on this neglected pathogen. 相似文献142.
The calcium-activated cysteine protease m-calpain plays a pivotal role during the earlier stages of myogenesis, particularly during fusion. The enzyme is a heterodimer, encoded by the genes capn2, for the large subunit, and capn4, for the small subunit. To study the regulation of m-calpain, the DNA sequence upstream of capn2 was analyzed for promoter elements, revealing the existence of five consensus-binding sites (E-box) for several myogenic regulatory factors and one binding site for myocyte enhancer factor-2 (MEF-2). Transient transfections with reporter gene constructs containing the E-box revealed that MyoD presents a high level of transactivation of reporter constructs containing this region, in particular the sequences including the MEF-2/E4-box. In addition, over-expression of various myogenic factors demonstrated that MyoD and myogenin with much less efficiency, can up-regulate capn2, both singly and synergistically, while Myf5 has no effect on synthesis of the protease. Experiments with antisense oligonucleotides directed against each myogenic factor revealed that MyoD plays a specific and pivotal role during capn2 regulation, and cannot be replaced wholly by myogenin and Myf5. 相似文献
143.
Dedieu S Dourdin N Dargelos E Poussard S Veschambre P Cottin P Brustis JJ 《Biology of the cell / under the auspices of the European Cell Biology Organization》2002,94(2):65-76
Previous studies have led us to hypothesize that m-calpain plays a pivotal role in myoblast fusion through its involvement in cell membrane and cytoskeleton component reorganization. To support this hypothesis, a convenient and simple myoblast culture model using frozen embryonic myoblasts was developed, which resolved a number of problems inherent to cell primary culture. Biological assays on cultured myoblasts using different media to define the characteristics of the fusion process were first conducted. Proteinase was detectable before the initiation of the fusion process and was closely correlated to the phenomenon of fusion under each culture condition studied. In addition, the study of calpastatin showed that the initiation of fusion does not require a decrease in the level of this endogenous inhibitor of calpains and also confirmed that calpastatin may be implicated in the determination of the end of fusion. On the other hand, analysis of the evolution of myogenic factors revealed that myogenins, MyoD and Myf5, increase very significantly during the formation of multinucleated myotubes. Moreover, the antisense technique against myogenin is capable of preventing the process of fusion by 50%, confirming the pivotal role of this factor in the early stages of differentiation. The possible role of myogenic regulator factors on m-calpain gene expression is discussed. 相似文献
144.
N-ethylmaleimide-sensitive factor is required to organize functional exocytotic microdomains in paramecium 总被引:2,自引:0,他引:2
In exocytosis, secretory granules contact plasma membrane at sites where microdomains can be observed, which are sometimes marked by intramembranous particle arrays. Such arrays are particularly obvious when membrane fusion is frozen at a subterminal stage, e.g., in neuromuscular junctions and ciliate exocytotic sites. In Paramecium, a genetic approach has shown that the "rosettes" of intramembranous particles are essential for stimulated exocytosis of secretory granules, the trichocysts. The identification of two genes encoding the N-ethylmaleimide-sensitive factor (NSF), a chaperone ATPase involved in organelle docking, prompted us to analyze its potential role in trichocyst exocytosis using a gene-silencing strategy. Here we show that NSF deprivation strongly interferes with rosette assembly but does not disturb the functioning of exocytotic sites already formed. We conclude that rosette organization involves ubiquitous partners of the fusion machinery and discuss where NSF could intervene in this mechanism. 相似文献
145.
Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion 总被引:32,自引:4,他引:28
Simple but exact statistical tests for detecting a cluster of associated
nucleotide changes in DNA are presented. The tests are based on the linear
distribution of a set of s sites among a total of n sites, where the s
sites may be the variable sites, sites of insertion/deletion, or
categorized in some other way. These tests are especially useful for
detecting gene conversion and intragenic recombination in a sample of DNA
sequences. In this case, the sites of interest are those that correspond to
particular ways of splitting the sequences into two groups (e.g., sequences
A and D vs. sequences B, C, and E-J). Each such split is termed a
phylogenetic partition. Application of these methods to a well-documented
case of gene conversion in human gamma-globin genes shows that sites
corresponding to two of the three observed partitions are significantly
clustered, whereas application to hominoid mitochondrial DNA
sequences--among which no recombination is expected to occur--shows no
evidence of such clustering. This indicates that clustering of
partition-specific sites is largely due to intragenic recombination or gene
conversion. Alternative hypotheses explaining the observed clustering of
sites, such as biased selection or mutation, are discussed.
相似文献
146.
The nucleotide sequences of the cow epsilon 2 and epsilon 4 globin genes
were determined. The sequences were 95% identical. These genes arose via a
four-gene block duplication that also gave rise to the bovine fetal (gamma)
and adult (beta) genes. Their deduced amino acid sequences are unlike any
previously reported fetal or adult globins; rather, comparison to other
mammalian globin genes indicates that they are embryonic in nature. The
sequence data indicate that these two genes have converted each other
during evolution. Pairwise comparison to the corresponding goat genes shows
greater similarity between paralogues than between more directly related
orthologues. This is in direct contrast to the situation between the cow
and goat fetal and adult genes. These observations suggest that the
frequency of DNA conversion or the fixation of conversion events may vary
in different locations of the cow beta-globin cluster.
相似文献
147.
148.
149.
Human responses to propionic acid. I. Quantification of within- and between-participant variation in perception by normosmics and anosmics 总被引:4,自引:3,他引:1
The objective of this study was to fully characterize normosmic perception
of stimuli expected to cause widely varying degrees of olfactory and nasal
trigeminal stimulation and to directly evaluate the possible role of
olfactory nerve stimulation in nasal irritation sensitivity. During each of
four identical test sessions, four anosmic and 31 normosmic participants
were presented with a range of concentrations extending from peri-threshold
for normosmics to supra- threshold for anosmics. For each session, odor (O)
and nasal irritation (NI) sensitivities were summarized in terms of the
concentrations required to produce four sensation levels ('iso-response'
concentrations). Within-participant variation in these iso-response
concentrations was < 10-fold for 95% of normosmics, for both O and NI.
For O but not NI, these apparent fluctuations in sensitivity were largely
accounted for by the uncertainty surrounding the iso-response
concentrations calculated for each session. Anosmics exhibited minimal
within- and between-participant variation in NI and required, for all but
the highest perceptual level, a higher concentration than almost all
normosmics. Between-participant variation, expressed in terms of 90%
confidence interval widths, was approximately 0.5 log units for both O and
NI for the highest perceptual level, but increased to approximately 0.8 and
1.8 log units, respectively, for the lowest (peri- threshold) level. Our
findings suggest that: (i) most apparent variation over time in O
sensitivity is actually a reflection of the uncertainty surrounding
estimates of sensitivity obtained for each session; (ii) within- and
between-participant variation in O sensitivity is far less than is commonly
reported; and (iii) low to moderate levels of NI in normosmics are the
result of relatively weak trigeminal stimulation combined with much greater
olfactory activation.
相似文献
150.
Regier JC; Fang QQ; Mitter C; Peigler RS; Friedlander TP; Solis MA 《Molecular biology and evolution》1998,15(9):1172-1182
Evolution and phylogenetic utility of the period gene are explored through
sequence analysis of a relatively conserved 909-bp fragment in 26
lepidopteran species. Taxa range from tribes to superfamilies, primarily
within the putative clade Macrolepidotera plus near outgroups, and include
both strongly established and problematic groupings. Their divergence dates
probably range from the late Cretaceous through much of the Tertiary.
Comparisons within the same set of closely related species show that amino
acid substitutions in period occur 4.9 and 44 times as frequently as they
do in two other nuclear genes--dopa decarboxylase and elongation factor-1
alpha, respectively. In contrast, rates of observed synonymous substitution
are within 60% of each other for these three genes. Synonymous changes in
period approach saturation by the family level, whereas nonsynonymous and
amino acid divergences across the Macrolepidoptera are less than half the
maximal values reported for this gene. Phylogenetic analyses of period
strongly supported groupings at the family level and below. In contrast to
previous analyses at this level with other nuclear genes, much of the
information lies in nonsynonymous change. Relationships up to the
superfamily level were recovered with decreasing effectiveness, and little,
if any, signal was apparent regarding relationships among superfamilies.
This could reflect rapid radiation of the superfamilies, however, rather
than saturation in the period locus; thus, period, in combination with
other genes, remains a plausible candidate for approaching the difficult
problems of lepidopteran family and superfamily relationships.
相似文献