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21.
The proteolytic processing of amyloid β precursor protein (APP) has long been studied because of its association with the pathology of Alzheimer's disease (AD). The ectodomain of APP is shed by α- or β-secretase cleavage. The remaining membrane bound stub can then undergo regulated intramembrane proteolysis (RIP) by γ-secretase. This cleavage can release amyloid β (Aβ) from the stub left by β-secretase cleavage but also releases the APP intracellular domain (AICD) after α- or β-secretase cleavage. The physiological functions of this proteolytic processing are not well understood. We compare the proteolytic processing of APP to the ligand-dependent RIP of Notch. In this review, we discuss recent evidence suggesting that TAG1 is a functional ligand for APP. The interaction between TAG1 and APP triggers γ-secretase-dependent release of AICD. TAG1, APP and Fe65 colocalise in the neurogenic ventricular zone and in fetal neural progenitor cells in vitro. Experiments in TAG1, APP and Fe65 null mice as well as TAG1 and APP double-null mice demonstrate that TAG1 induces a γ-secretase- and Fe65-dependent suppression of neurogenesis.  相似文献   
22.
Previous studies have shown that Sox3 is expressed in nascent neuroprogenitor cells and is functionally required in mammals for development of the dorsal telencephalon and hypothalamus. However, Sox3 expression during embryonic and adult neurogenesis has not been examined in detail. Using a SOX3-specific antibody, we show that murine SOX3 expression is maintained throughout telencephalic neurogenesis and is restricted to progenitor cells with neuroepithelial and radial glial morphologies. We also demonstrate that SOX3 is expressed within the adult neurogenic regions and is coexpressed extensively with the neural stem cell marker SOX2 indicating that it is a lifelong marker of neuroprogenitor cells. In contrast to the telencephalon, Sox3 expression within the developing hypothalamus is upregulated in developing neurons and is maintained in a subset of differentiated hypothalamic cells through to adulthood. Together, these data show that Sox3 regulation is region-specific, consistent with it playing distinct biological roles in the dorsal telencephalon and hypothalamus.  相似文献   
23.
ABSTRACT

Potent second-generation anticoagulant rodenticides such as brodifacoum have been used as more effective alternatives to first-generation anticoagulants, such as warfarin. A combination of diphacinone at 0.005% and cholecalciferol at 0.06% produces a slow-acting bait that is effective at killing possums (Trichosurus vulpecula) and rodents. Cage trials with groups of possums and ship rats (Rattus rattus) achieved a mortality of 87% and 86% for possums and ship rats, respectively. Two field trials, each 200 hectares in size, targeting possums, ship rats and mice achieved an average reduction in the abundance of 94% for possums, 94% for ship rats and 80% for mice. The combination of diphacinone and cholecalciferol appears effective and has a favourable risk profile compared with second-generation anticoagulant rodenticides, such as brodifacoum. Approval of this new bait by the New Zealand Environmental Protection Agency was granted in 2018 and final registration obtained from the Ministry of Primary Industries in 2019.  相似文献   
24.
Specialized microenvironment, or neurogenic niche, in embryonic and postnatal mouse brain plays critical roles during neurogenesis throughout adulthood. The subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus in the mouse brain are two major neurogenic niches where neurogenesis is directed by numerous regulatory factors. Now, we report Akhirin (AKH), a stem cell maintenance factor in mouse spinal cord, plays a pivotal regulatory role in the SVZ and in the DG. AKH showed specific distribution during development in embryonic and postnatal neurogenic niches. Loss of AKH led to abnormal development of the ventricular zone and the DG along with reduction of cellular proliferation in both regions. In AKH knockout mice (AKH−/−), quiescent neural stem cells (NSCs) increased, while proliferative NSCs or neural progenitor cells decreased at both neurogenic niches. In vitro NSC culture assay showed increased number of neurospheres and reduced neurogenesis in AKH−/−. These results indicate that AKH, at the neurogenic niche, exerts dynamic regulatory role on NSC self-renewal, proliferation and differentiation during SVZ and hippocampal neurogenesis.  相似文献   
25.
Abstract

Four control operations, each with paired pre‐feed and no‐pre‐feed treatments, and comprising two baited with carrot and two with cereal, provided strong support for the hypothesis that pre‐feeding produces higher possum kills than no pre‐feeding. In these replicates, even where high kills were achieved, the modelled two‐ to three‐fold extension of the period of population depression given by pre‐feeding was sufficient to warrant the expense of the additional bait sown. The benefits of pre‐feeding were clear‐cut, and were greatest where poorest kills were achieved, irrespective of bait type. Pre‐feeding is thus likely to reduce the probability of failure and should be considered a form of operational insurance.  相似文献   
26.
Hongbin Wang  Xi Chen  Teng He  Yanna Zhou  Hong Luo 《Genetics》2013,195(4):1291-1306
The evolutionarily conserved JAK/STAT pathway plays important roles in development and disease processes in humans. Although the signaling process has been well established, we know relatively little about what the relevant target genes are that mediate JAK/STAT activation during development. Here, we have used genome-wide microarrays to identify JAK/STAT targets in the optic lobes of the Drosophila brain and identified 47 genes that are positively regulated by JAK/STAT. About two-thirds of the genes encode proteins that have orthologs in humans. The STAT targets in the optic lobe appear to be different from the targets identified in other tissues, suggesting that JAK/STAT signaling may regulate different target genes in a tissue-specific manner. Functional analysis of Nop56, a cell-autonomous STAT target, revealed an essential role for this gene in the growth and proliferation of neuroepithelial stem cells in the optic lobe and an inhibitory role in lamina neurogenesis.  相似文献   
27.
In the adult mammalian brain, neural stem cells in the subventricular zone continuously generate new neurons for the olfactory bulb. Cell fate commitment in these adult neural stem cells is regulated by cell fate-determining proteins. Here, we show that the cell fate-determinant TRIM32 is upregulated during differentiation of adult neural stem cells into olfactory bulb neurons. We further demonstrate that TRIM32 is necessary for the correct induction of neuronal differentiation in these cells. In the absence of TRIM32, neuroblasts differentiate slower and show gene expression profiles that are characteristic of immature cells. Interestingly, TRIM32 deficiency induces more neural progenitor cell proliferation and less cell death. Both effects accumulate in an overproduction of adult-generated olfactory bulb neurons of TRIM32 knockout mice. These results highlight the function of the cell fate-determinant TRIM32 for a balanced activity of the adult neurogenesis process.  相似文献   
28.
  1. The development of encompassing general models of ecology is precluded by underrepresentation of certain taxa and systems. Models predicting context‐dependent outcomes of biotic interactions have been tested using plants and bacteria, but their applicability to higher taxa is largely unknown.
  2. We examined context dependency in a reproductive mutualism between two stream fish species: mound nest‐building bluehead chub Nocomis leptocephalus and mountain redbelly dace Chrosomus oreas, which often uses N. leptocephalus nests for spawning. We hypothesized that increased predator density and decreased substrate availability would increase the propensity of C. oreas to associate with N. leptocephalus and decrease reproductive success of both species.
  3. In a large‐scale in situ experiment, we manipulated egg predator density and presence of both symbionts (biotic context), and replicated the experiment in habitats containing high‐ and low‐quality spawning substrate (abiotic context).
  4. Contradictory to our first hypothesis, we observed that C. oreas did not spawn without its host. The interaction outcome switched from commensalistic to mutualistic with changing abiotic and biotic contexts, although the net outcome was mutualistic.
  5. The results of this study yielded novel insight into how context dependency operates in vertebrate mutualisms. Although the dilution effect provided by C. oreas positively influenced reproductive success of N. leptocephalus, it was not enough to overcome both egg predation and poor spawning habitat quality. Outcomes of the interaction may be ultimately determined by associate density. Studies of context dependency in vertebrate systems require detailed knowledge of species life‐history traits.
  相似文献   
29.
Neural progenitor cells have a central role in the development and evolution of the vertebrate brain. During early brain development, neural progenitors first expand their numbers through repeated proliferative divisions and then begin to exhibit neurogenic divisions. The transparent and experimentally accessible optic tectum of Xenopus laevis is an excellent model system for the study of the cell biology of neurogenesis, but the precise spatial and temporal relationship between proliferative and neurogenic progenitors has not been explored in this system. Here we construct a spatial map of proliferative and neurogenic divisions through lineage tracing of individual progenitors and their progeny. We find a clear spatial separation of proliferative and neurogenic progenitors along the anterior‐posterior axis of the optic tectum, with proliferative progenitors located more posteriorly and neurogenic progenitors located more anteriorly. Since individual progenitors are repositioned toward more anterior locations as they mature, this spatial separation likely reflects an increasing restriction in the proliferative potential of individual progenitors. We then examined whether the transition from proliferative to neurogenic behavior correlates with cellular properties that have previously been implicated in regulating neurogenesis onset. Our data reveal that the transition from proliferation to neurogenesis is associated with a small change in cleavage plane orientation and a more pronounced change in cell cycle kinetics in a manner reminiscent of observations from mammalian systems. Our findings highlight the potential to use the optic tectum of Xenopus laevis as an accessible system for the study of the cell biology of neurogenesis. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1328–1341, 2016  相似文献   
30.
Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo‐spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel‐specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, suggesting that niche blood vessels regulate NSC differentiation at least in part by providing oxygen. Consistent herewith, hypoxia‐inducible factor (HIF)‐1α levels controlled the switch of NSC expansion to differentiation. Finally, we provide evidence that high glycolytic activity of NSCs is required to prevent their precocious differentiation in vivo. Thus, blood vessel function is required for efficient NSC differentiation in the developing cerebral cortex by providing oxygen and possibly regulating NSC metabolism.  相似文献   
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