全文获取类型
收费全文 | 3905篇 |
免费 | 398篇 |
国内免费 | 1篇 |
专业分类
4304篇 |
出版年
2021年 | 34篇 |
2018年 | 41篇 |
2017年 | 36篇 |
2016年 | 68篇 |
2015年 | 106篇 |
2014年 | 131篇 |
2013年 | 149篇 |
2012年 | 197篇 |
2011年 | 230篇 |
2010年 | 144篇 |
2009年 | 122篇 |
2008年 | 199篇 |
2007年 | 195篇 |
2006年 | 210篇 |
2005年 | 229篇 |
2004年 | 220篇 |
2003年 | 186篇 |
2002年 | 215篇 |
2001年 | 38篇 |
2000年 | 24篇 |
1999年 | 51篇 |
1998年 | 71篇 |
1997年 | 61篇 |
1996年 | 43篇 |
1995年 | 47篇 |
1994年 | 45篇 |
1993年 | 43篇 |
1992年 | 30篇 |
1991年 | 26篇 |
1990年 | 22篇 |
1989年 | 31篇 |
1988年 | 26篇 |
1987年 | 36篇 |
1986年 | 23篇 |
1985年 | 42篇 |
1984年 | 47篇 |
1983年 | 32篇 |
1982年 | 51篇 |
1981年 | 47篇 |
1980年 | 52篇 |
1979年 | 51篇 |
1978年 | 37篇 |
1977年 | 36篇 |
1976年 | 37篇 |
1975年 | 31篇 |
1974年 | 33篇 |
1973年 | 35篇 |
1970年 | 20篇 |
1969年 | 22篇 |
1968年 | 21篇 |
排序方式: 共有4304条查询结果,搜索用时 15 毫秒
91.
Scholten JC Culley DE Brockman FJ Wu G Zhang W 《Biochemical and biophysical research communications》2007,352(1):48-54
The sulfate reducing bacteria Desulfovibrio vulgaris and the methanogenic archaea Methanosarcina barkeri can grow syntrophically on lactate. In this study, a set of three closely located genes, DVU2103, DVU2104, and DVU2108 of D. vulgaris, was found to be up-regulated 2- to 4-fold following the lifestyle shift from syntroph to sulfate reducer; moreover, none of the genes in this gene set were differentially regulated when comparing gene expression from various D. vulgaris pure culture experiments. Although exact function of this gene set is unknown, the results suggest that it may play roles related to the lifestyle change of D. vulgaris from syntroph to sulfate reducer. This hypothesis is further supported by phylogenomic analyses showing that homologies of this gene set were only narrowly present in several groups of bacteria, most of which are restricted to a syntrophic lifestyle, such as Pelobacter carbinolicus, Syntrophobacter fumaroxidans, Syntrophomonas wolfei, and Syntrophus aciditrophicus. Phylogenetic analysis showed that all three individual genes in the gene set tended to be clustered with their homologies from archaeal genera, and they were rooted on archaeal species in the phylogenetic trees, suggesting that they were horizontally transferred from archaeal methanogens. In addition, no significant bias in codon and amino acid usages was detected between these genes and the rest of the D. vulgaris genome, suggesting the gene transfer may have occurred early in the evolutionary history so that sufficient time has elapsed to allow an adaptation to the codon and amino acid usages of D. vulgaris. This report provides novel insights into the origin and evolution of bacterial genes linked to the lifestyle change of D. vulgaris from a syntrophic to a sulfate-reducing lifestyle. 相似文献
92.
Hickman AB Perez ZN Zhou L Musingarimi P Ghirlando R Hinshaw JE Craig NL Dyda F 《Nature structural & molecular biology》2005,12(8):715-721
Mobile elements and their inactive remnants account for large proportions of most eukaryotic genomes, where they have had central roles in genome evolution. Over 50 years ago, McClintock reported a form of stress-induced genome instability in maize in which discrete DNA segments move between chromosomal locations. Our current mechanistic understanding of enzymes catalyzing transposition is largely limited to prokaryotic transposases. The Hermes transposon from the housefly is part of the eukaryotic hAT superfamily that includes hobo from Drosophila, McClintock's maize Activator and Tam3 from snapdragon. We report here the three-dimensional structure of a functionally active form of the transposase from Hermes at 2.1-A resolution. The Hermes protein has some structural features of prokaryotic transposases, including a domain with a retroviral integrase fold. However, this domain is disrupted by the insertion of an additional domain. Finally, transposition is observed only when Hermes assembles into a hexamer. 相似文献
93.
Dynamic properties of microtubules contribute to the establishment of spatial order within cells. In the fission yeast Schizosaccharomyces pombe, interphase cytoplasmic microtubules are organized into antiparallel bundles that attach to the nuclear envelope and are needed to position the nucleus at the geometric center of the cell. Here, we show that after the nucleus is displaced by cell centrifugation, these microtubule bundles efficiently push the nucleus back to the center. Asymmetry in microtubule number, length, and dynamics contributes to the generation of force responsible for this unidirectional movement. Notably, microtubules facing the distal cell tip are destabilized when the microtubules in the same bundle are pushing from the proximal cell tip. The CLIP-170-like protein tip1p and the microtubule-bundling protein ase1p are required for this asymmetric regulation of microtubule dynamics, indicating contributions of factors both at microtubule plus ends and within the microtubule bundle. Mutants in these factors are defective in nuclear movement. Thus, cells possess an efficient microtubule-based engine that produces and senses forces for centering the nucleus. These studies may provide insights into mechanisms of asymmetric microtubule behaviors and force sensing in other processes such as chromosome segregation and cell polarization. 相似文献
94.
Maarten A. Jongsma Fred Gould Mathieu Legros Limei Yang Joop J. A. van Loon Marcel Dicke 《Evolutionary ecology》2010,24(5):1017-1030
The major lepidopteran insect pests of cotton and maize harbor intra-specific variation for behavior determining the selection
of host plants for oviposition. Yet, the consequences of behavioral adaptation for fitness have neither been modeled nor monitored
for Bt cotton and maize crops, the most widely grown transgenic herbivore-resistant plants. Here, we present a general two-locus
heuristic model to examine potential outcomes of natural selection when pest populations initially have low frequencies of
alleles for both physiological and behavioral adaptation to Bt crops. We demonstrate that certain ecological conditions allow for the evolution of behavioral choices favoring alternative
oviposition hosts that limit the increase in resistance alleles, even when they are phenotypically dominant. These results
have implications for current refuge policies, which should be adapted to promote the evolution of certain behavioral choices
for alternative oviposition hosts in addition to dilution of physiological resistance alleles. Collection of data on oviposition
host preference as a component of monitoring schemes will provide important insights into mechanisms underlying the durability
of Bt-transgenic host-plant resistance. 相似文献
95.
Amanda D. Melin Brooke E. Crowley Shaun T. Brown Patrick V. Wheatley Gillian L. Moritz Fred Tuh Yit Yu Henry Bernard Donald J. DePaolo Andrew D. Jacobson Nathaniel J. Dominy 《American journal of physical anthropology》2014,154(4):633-643
Calcium stable isotope ratios are hypothesized to vary as a function of trophic level. This premise raises the possibility of using calcium stable isotope ratios to study the dietary behaviors of fossil taxa and to test competing hypotheses on the adaptive origins of euprimates. To explore this concept, we measured the stable isotope composition of contemporary mammals in northern Borneo and northwestern Costa Rica, two communities with functional or phylogenetic relevance to primate origins. We found that bone collagen δ13C and δ15N values could differentiate trophic levels in each assemblage, a result that justifies the use of these systems to test the predicted inverse relationship between bioapatite δ13C and δ44Ca values. As expected, taxonomic carnivores (felids) showed a combination of high δ13C and low δ44Ca values; however, the δ44Ca values of other faunivores were indistinguishable from those of primary consumers. We suggest that the trophic insensitivity of most bioapatite δ44Ca values is attributable to the negligible calcium content of arthropod prey. Although the present results are inconclusive, the tandem analysis of δ44Ca and δ13C values in fossils continues to hold promise for informing paleodietary studies and we highlight this potential by drawing attention to the stable isotope composition of the Early Eocene primate Cantius. Am J Phys Anthropol 154:633–643, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
96.
Ma X Lin Y Lin L Qin G Pereira FA Haymond MW Butte NF Sun Y 《American journal of physiology. Endocrinology and metabolism》2012,303(3):E422-E431
The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion. Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia. The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes. However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion. We investigated the effects of GHS-R on glucose homeostasis in Ghsr-ablated ob/ob mice (Ghsr(-/-):ob/ob). Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice. Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance. Consistently, Ghsr ablation in ob/ob mice upregulated negative β-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive β-cell regulators (such as HIF-1α, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic β-cell function in leptin deficiency. Of note, Ghsr ablation in ob/ob mice did not affect the islet size; the average islet size of Ghsr(-/-):ob/ob mice is similar to that of ob/ob mice. In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions. The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway. 相似文献
97.
Cross-sectional areas of human frontal sinuses in the occipitofrontal projection are a good surrogate for frontal sinus volumes. This study looks at these areas in a dataset of some 200 children and 100 adults of both sexes. As measured by planimetry of roentgenograms, the areas are extremely variable ("noisy" in a statistical sense). In fact, they appear to be distributed log-normally with quite high variance. The mean of the distribution is evidently a function of age and the variances differ by sex. After logarithmic transformation, the data are adequately fitted by one sigmoid curve for each sex. Our discussion highlights implications of this finding for the biological aspects of frontal sinuses and methodological issues in ontogenetic analysis of data so noisy. 相似文献
98.
WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility 总被引:11,自引:0,他引:11
Yan C Martinez-Quiles N Eden S Shibata T Takeshima F Shinkura R Fujiwara Y Bronson R Snapper SB Kirschner MW Geha R Rosen FS Alt FW 《The EMBO journal》2003,22(14):3602-3612
The Wiskott-Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement. 相似文献
99.
THE STRUCTURAL BASIS OF CILIARY BEND FORMATION : Radial Spoke Positional Changes Accompanying Microtubule Sliding 总被引:10,自引:27,他引:10 下载免费PDF全文
The sliding microtubule model of ciliary motility predicts that cumulative local displacement (Δl) of doublet microtubules relative to one another occurs only in bent regions of the axoneme. We have now tested this prediction by using the radial spokes which join the A subfiber of each doublet to the central sheath as markers of microtubule alignment to measure sliding displacements directly. Gill cilia from the mussel Elliptio complanatus have radial spokes lying in groups of three which repeat at 860 Å along the A subfiber. The spokes are aligned with the two rows of projections along each of the central microtubules that form the central sheath. The projections repeat at 143 Å and form a vernier with the radial spokes in the precise ratio of 6 projection repeats to 1 spoke group repeat. In straight regions of the axoneme, either proximal or distal to a bend, the relative position of spoke groups between any two doublets remains constant for the length of that region. However, in bent regions, the position of spoke groups changes systematically so that Δl (doublet 1 vs. 5) can be seen to accumulate at a maximum of 122 Å per successive 860-Å spoke repeat. Local contraction of microtubules is absent. In straight regions of the axoneme, the radial spokes lie in either of two basic configurations: (a) the parallel configuration where spokes 1–3 of each group are normal (90°) to subfiber A, and (b) the tilted spoke 3 configuration where spoke 3 forms an angle (θ) of 9–20°. Since considerable sliding of doublets relative to the central sheath (~650 Å) has usually occurred in these regions, the spokes must be considered, functionally, as detached from the sheath projections. In bent regions of the axoneme, two additional spoke configurations occur where all three spokes of each group are tilted to a maximum of ± 33° from normal. Since the spoke angles do not lie on radii through the center of bend curvature, and Δl accumulates in the bend, the spokes must be considered as attached to the sheath when bending occurs. The observed radial spoke configurations strongly imply that there is a precise cycle of spoke detachment-reattachment to the central sheath which we conclude forms the main part of the mechanism converting active interdoublet sliding into local bending. 相似文献
100.