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191.
Cristina D. Orrù Claudia Abete M. Dolores Cannas Claudia Mulas Claudia Norfo Antonella Mandas Sarah Vascellari Paolo La Colla Sandra Dessì Alessandra Pani 《Central European Journal of Biology》2010,5(1):31-37
Scrapie is a prion disease for which no means of ante-mortem diagnosis is available. We recently found a relationship between
cell susceptibility to scrapie and altered cholesterol homeostasis. In brains and in skin fibroblasts and peripheral blood
mononuclear cells from healthy and scrapie-affected sheep carrying a scrapie-susceptible genotype, the levels of cholesterol
esters were consistently higher than in tissues and cultures derived from animals with a scrapie-resistant genotype. Here
we show that intracellular accumulation of cholesterol esters (CE) in fibroblasts derived from scrapie-susceptible sheep was
accompanied by parallel alterations in the expression level of acyl-coenzymeA: cholesterol-acyltransferase (ACAT1) and caveolin-1
(Cav-1) that are involved in the pathways leading to intracellular cholesterol esterification and trafficking. Comparative
analysis of cellular prion protein (PrPc) mRNA, showed an higher expression level in cells from animals carrying a susceptible
genotype, with or without Scrapie. These data suggest that CE accumulation in peripheral cells, together with the altered
expression of some proteins implicated in intracellular cholesterol homeostasis, might serve to identify a distinctive lipid
metabolic profile associated with increased susceptibility to develop prion disease following infection. 相似文献
192.
Background
Large-scale gene expression studies have not yielded the expected insight into genetic networks that control complex processes. These anticipated discoveries have been limited not by technology, but by a lack of effective strategies to investigate the data in a manageable and meaningful way. Previous work suggests that using a pre-determined seed-network of gene relationships to query large-scale expression datasets is an effective way to generate candidate genes for further study and network expansion or enrichment. Based on the evolutionary conservation of gene relationships, we test the hypothesis that a seed network derived from studies of retinal cell determination in the fly, Drosophila melanogaster, will be an effective way to identify novel candidate genes for their role in mouse retinal development.Methodology/Principal Findings
Our results demonstrate that a number of gene relationships regulating retinal cell differentiation in the fly are identifiable as pairwise correlations between genes from developing mouse retina. In addition, we demonstrate that our extracted seed-network of correlated mouse genes is an effective tool for querying datasets and provides a context to generate hypotheses. Our query identified 46 genes correlated with our extracted seed-network members. Approximately 54% of these candidates had been previously linked to the developing brain and 33% had been previously linked to the developing retina. Five of six candidate genes investigated further were validated by experiments examining spatial and temporal protein expression in the developing retina.Conclusions/Significance
We present an effective strategy for pursuing a systems biology approach that utilizes an evolutionary comparative framework between two model organisms, fly and mouse. Future implementation of this strategy will be useful to determine the extent of network conservation, not just gene conservation, between species and will facilitate the use of prior biological knowledge to develop rational systems-based hypotheses. 相似文献193.
Orr MT Wu J Fang M Sigal LJ Spee P Egebjerg T Dissen E Fossum S Phillips JH Lanier LL 《PloS one》2010,5(12):e15184
The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A subunit to form an inhibitory receptor or with the NKG2C or NKG2E subunits to assemble a receptor complex with activating DAP12 signaling proteins. CD94 receptors expressed on human and mouse NK cells and T cells have been proposed to be important in NK cell tolerance to self, play an important role in NK cell development, and contribute to NK cell-mediated immunity to certain infections including human cytomegalovirus. We generated a gene-targeted CD94-deficient mouse to understand the role of CD94 receptors in NK cell biology. CD94-deficient NK cells develop normally and efficiently kill NK cell-susceptible targets. Lack of these CD94 receptors does not alter control of mouse cytomegalovirus, lymphocytic choriomeningitis virus, vaccinia virus, or Listeria monocytogenes. Thus, the expression of CD94 and its associated NKG2A, NKG2C, and NKG2E subunits is dispensable for NK cell development, education, and many NK cell functions. 相似文献
194.
195.
Eitan Ben-Dov Nachshon Siboni Orr H. Shapiro Luba Arotsker Ariel Kushmaro 《Microbial ecology》2011,61(1):1-6
Universal 16S rRNA gene primers (8F and 518R) bearing inosine substitutions at either the 3??-ultimate or the 3??-ultimate and penultimate base positions were exploited for the first time to study the bacterial community associated with coral polymicrobial Black Band Disease (BBD). Inosine-modified universal primer pairs display some shifting in the composition of 16S rRNA gene libraries, as well as expanding the observed diversity of a BBD bacterial community at the family/class level. Possible explanations for the observed shifts are discussed. These results thus point to the need for adopting multiple approaches in designing 16S rRNA universal primers for PCR amplification and subsequent construction of 16S rRNA gene libraries or pyrosequencing in the exploration of complex microbial communities. 相似文献
196.
Probing conformational changes of gramicidin ion channels by single-molecule patch-clamp fluorescence microscopy
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Complex conformational changes influence and regulate the dynamics of ion channels. Such conformational changes are stochastic and often inhomogeneous, which makes it extremely difficult, if not impossible, to characterize them by ensemble-averaged experiments or by single-channel recordings of the electric current that report the open-closed events but do not specifically probe the associated conformational changes. Here, we report our studies on ion channel conformational changes using a new approach, patch-clamp fluorescence microscopy, which simultaneously combines single-molecule fluorescence spectroscopy and single-channel current recordings to probe the open-closed transitions and the conformational dynamics of individual ion channels. We demonstrate patch-clamp fluorescence microscopy by measuring gramicidin ion channel conformational changes in a lipid bilayer formed at a patch-clamp micropipette tip under a buffer solution. By measuring single-pair fluorescence resonance energy transfer and fluorescence self-quenching from dye-labeled gramicidin channels, we observed that the efficiency of single-pair fluorescence resonance energy transfer and self-quenching is widely distributed, which reflects a broad distribution of conformations. Our results strongly suggest a hitherto undetectable correlation between the multiple conformational states of the gramicidin channel and its closed and open states in a lipid bilayer. 相似文献
197.
198.
While Bacillus thuringiensis subsp. israelensis de Barjac, 1978 (Bti) is generally effective in reducing Simulium Latreille, 1802 pest levels, impaired toxicity has been identified. Diatoms are typically abundant in Simulium larval gut contents and thought to affect feeding behaviour and/or Bti ingestion. We sought to determine diatom composition in larval Simulium gut contents and periphyton in relation to mortality subsequent in situ Bti application across three stream reaches. Generally, lower larval mortality after Bti exposure was associated with comparatively greater diatom diversity inside gut contents, corresponding with an inverse relationship between periphyton diatom diversity and larval mortality across our study reaches. High profile diatoms inside gut contents were positively correlated with mortality, suggesting microbial morphology may affect Bti efficacy. Diatoms inside live larval guts were most similar to periphyton which indicates that these larvae may have been feeding less on lower quality detrital material and/or exhibiting comparatively greater benthic feeding. 相似文献
199.