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1.
The evolution of hypermutators in response to antibiotic treatment in both clinical and laboratory settings provides a unique context for the study of adaptive evolution. With increased mutation rates, the number of hitchhiker mutations within an evolving hypermutator population is remarkably high and presents substantial challenges in determining which mutations are adaptive. Intriguingly however, hypermutators also provide an opportunity to explore deeply the accessible evolutionary trajectories that lead to increased organism fitness, in this case the evolution of antibiotic resistance to the clinically relevant antibiotic tigecycline by the hospital pathogen Acinetobacter baumannii. Using a continuous culture system, AB210M, a clinically derived strain of A. baumannii, was evolved to tigecycline resistance. Analysis of the adapted populations showed that nearly all the successful lineages became hypermutators via movement of a mobile element to inactivate mutS. In addition, metagenomic analysis of population samples revealed another 896 mutations that occurred at a frequency greater than 5% in the population, while 38 phenotypically distinct individual colonies harbored a total of 1712 mutations. These mutations were scattered throughout the genome and affected ~40% of the coding sequences. The most highly mutated gene was adeS, a known tigecycline-resistance gene; however, adeS was not solely responsible for the high level of TGC resistance. Sixteen other genes stood out as potentially relevant to increased resistance. The five most prominent candidate genes (adeS, rpsJ, rrf, msbA, and gna) consistently re-emerged in subsequent replicate population studies suggesting they are likely to play a role in adaptation to tigecycline. Interestingly, the repeated evolution of a hypermutator phenotype in response to antibiotic stress illustrates not only a highly adaptive strategy to resistance, but also a remarkably efficient survey of successful evolutionary trajectories.  相似文献   
2.
Date palm (Phoenix dactylifera L.) is qualified as a 'tree' of great ecological and socio-economical importance in desert oases. Unfortunately, it is being decimated, especially in Morocco and Algeria, by a fusariosis wilt called bayoud and caused by Fusarium oxysporum f. sp. albedinis (Fao). Controlling this disease requires the implementation of an integrated management program. Breeding for resistance is one of the most promising component strategies of this program. Few naturally resistant cultivars with a mediocre fruit quality (dates) are known. Conventional and non-conventional methods are under development and have to use the simplest and easiest methods to screen for resistant individuals. The use of pathogen toxins as selective agents at the tissue culture step might be a source of variability that can lead to the selection of individuals with suitable levels of resistance to the toxin and/or to the pathogen among the genetic material available. Foa produces toxins such as fusaric, succinic, 3-phenyl lactic acids and their derivatives, marasmins and peptidic toxins. These toxins can be used bulked or separately as selective agents. The aim of this contribution was to give a brief overview on toxins and their use as a mean to select resistant lines and to initiate a discussion about the potential use of this approach for the date palm-Foa pathosystem. This review does not pretend to be comprehensive or exhaustive and was prepared mainly to highlight the potential use of Foa toxins for selecting date palm individuals with a suitable resistance level to bayoud using toxin-based selective media.  相似文献   
3.
    
There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is in MXL, in CLM, and in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern America ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas thousand years ago (kya), supports that the MXL Ancestors split kya, with a subsequent split of the ancestors to CLM and PUR kya. The model also features effective populations of in Mexico, in Colombia, and in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations.  相似文献   
4.
    
Diabetes mellitus is associated with vascular complications, including an impairment of vascular function and alterations in the reactivity of blood vessels to vasoactive agents. Phosphatidylinositol 3-kinase (PI3K) is a signalling enzyme that plays key roles in vascular growth, proliferation and cellular apoptosis and is implicated in modulating vascular smooth muscle contractility. The aim of this study was to determine whether PI3K plays a role in development of diabetes-induced altered vascular reactivity to selected vasoconstrictors and vasodilators. The effect of 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a selective PI3K inhibitor, on isolated segments of carotid arteries from streptozotocin (STZ)-diabetic rats was investigated. Ring segments of the isolated carotid arteries were mounted in organ baths to measure changes in isometric tension. Our results showed that STZ treatment produced an increase in the vasoconstrictor response to norepinephrine (NE), angiotensin II (Ang II) and endothelin-1 (ET-1) and an attenuated vasodilator response to carbachol and histamine in the isolated carotid arteries from STZ-diabetic animals. Diabetes-induced impaired vascular responsiveness to the vasoactive agonists was prevented by chronic inhibition of PI3K by LY294002 even though blood glucose levels remained high. This is the first study to show that selective inhibition of PI3K can attenuate the development of diabetes-induced abnormal vascular reactivity in the isolated carotid arteries of diabetic rats.  相似文献   
5.
  总被引:2,自引:0,他引:2  
Verticillium dahliae is a soilborne fungus that causes a vascular wilt disease of plants and losses in a broad range of economically important crops worldwide. In this study, we compared the proteomes of highly (Vd1396‐9) and weakly (Vs06‐14) aggressive isolates of V. dahliae to identify protein factors that may contribute to pathogenicity. Twenty‐five protein spots were consistently observed as differential in the proteome profiles of the two isolates. The protein sequences in the spots were identified by LC‐ESI‐MS/MS and MASCOT database searches. Some of the identified sequences shared homology with fungal proteins that have roles in stress response, colonization, melanin biosynthesis, microsclerotia formation, antibiotic resistance, and fungal penetration. These are important functions for infection of the host and survival of the pathogen in soil. One protein found only in the highly aggressive isolate was identified as isochorismatase hydrolase, a potential plant‐defense suppressor. This enzyme may inhibit the production of salicylic acid, which is important for plant defense response signaling. Other sequences corresponding to potential pathogenicity factors were identified in the highly aggressive isolate. This work indicates that, in combination with functional genomics, proteomics‐based analyses can provide additional insights into pathogenesis and potential management strategies for this disease.  相似文献   
6.
    
Calmodulin regulates ryanodine receptor-mediated Ca(2+) release through a conserved binding site. The crystal structure of Ca(2+)-calmodulin bound to this conserved site reveals that calmodulin recognizes two hydrophobic anchor residues at a novel \"1-17\" spacing that brings the calmodulin lobes close together but prevents them from contacting one another. NMR residual dipolar couplings demonstrate that the detailed structure of each lobe is preserved in solution but also show that the lobes experience domain motions within the complex. FRET measurements confirm the close approach of the lobes in binding the 1-17 target and show that calmodulin binds with one lobe to a peptide lacking the second anchor. We suggest that calmodulin regulates the Ca(2+) channel by switching between the contiguous binding mode seen in our crystal structure and a state where one lobe of calmodulin contacts the conserved binding site while the other interacts with a noncontiguous site on the channel.  相似文献   
7.
8.
Dyskinesias are hyperkinetic and involuntary movements that may result from any of a number of different genetic, infectious, and drug-induced causes. Some of the hereditary dyskinetic syndromes are characterized by paroxysmal onset of the abnormal movements. The classification of the familial paroxysmal dyskinesias (FPD) recognizes several distinct, although overlapping, phenotypes. Different forms of the disorder include attacks that are (1) induced by sudden movement (kinesiogenic); (2) spontaneous (non-kinesiogenic); and (3) induced by prolonged periods of exertion. Linkage analysis was pursued in a family segregating an autosomal dominant allele for non-kinesiogenic FPD. The disease allele was mapped to a locus on chromosome 2q31-36 (LOD score 4.64, theta = 0). Identification of distinct genetic loci for the paroxysmal dyskinesias will lead to a new genetic classification and to better understanding of these disorders.  相似文献   
9.
 Halophytes from both coastal and inland Central European salt marshes were examined for colonization by arbuscular mycorrhizal (AM) fungi. Plants from different families were strongly colonized but the degree of colonization varied with the individual plant and apparently during the vegetation period, too. Members of the typical non-mycorrhizal families like Armeria maritima of the Plumbaginaceae and Salicornia europaea of the Chenopodiaceae were found to be colonized, particularly in the drier salt marshes. High numbers of Glomus spores were found in the saline soils, especially those of the inland locations examined. Approximately 80% of these spores were from Glomus geosporum as shown by a typical restriction fragment length polymorphism (RFLP) pattern of the amplified internal transcribed spacer regions. The present study demonstrates that RFLP analysis is useful when screening habitats for the occurrence of mycorrhizal fungi which can be identified only with difficulty by morphological criteria. Accepted: 25 August 2000  相似文献   
10.
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