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991.
Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors 总被引:19,自引:0,他引:19 下载免费PDF全文
Dove SK Piper RC McEwen RK Yu JW King MC Hughes DC Thuring J Holmes AB Cooke FT Michell RH Parker PJ Lemmon MA 《The EMBO journal》2004,23(9):1922-1933
Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), made by Fab1p, is essential for vesicle recycling from vacuole/lysosomal compartments and for protein sorting into multivesicular bodies. To isolate PtdIns(3,5)P2 effectors, we identified Saccharomyces cerevisiae mutants that display fab1delta-like vacuole enlargement, one of which lacked the SVP1/YFR021w/ATG18 gene. Expressed Svp1p displays PtdIns(3,5)P2 binding of exquisite specificity, GFP-Svp1p localises to the vacuole membrane in a Fab1p-dependent manner, and svp1delta cells fail to recycle a marker protein from the vacuole to the Golgi. Cells lacking Svp1p accumulate abnormally large amounts of PtdIns(3,5)P2. These observations identify Svp1p as a PtdIns(3,5)P2 effector required for PtdIns(3,5)P2-dependent membrane recycling from the vacuole. Other Svp1p-related proteins, including human and Drosophila homologues, bind PtdIns(3,5)P2 similarly. Svp1p and related proteins almost certainly fold as beta-propellers, and the PtdIns(3,5)P2-binding site is on the beta-propeller. It is likely that many of the Svp1p-related proteins that are ubiquitous throughout the eukaryotes are PtdIns(3,5)P2 effectors. Svp1p is not involved in the contributions of FAB1/PtdIns(3,5)P2 to MVB sorting or to vacuole acidification and so additional PtdIns(3,5)P2 effectors must exist. 相似文献
992.
Evans MD Cooke MS 《BioEssays : news and reviews in molecular, cellular and developmental biology》2004,26(5):533-542
Oxidative damage to DNA appears to be a factor in cancer, yet explanations for why highly elevated levels of such lesions do not always result in cancer remain elusive. Much of the genome is non-coding and lesions in these regions might be expected to have little biological effect, an inference supported by observations that there is preferential repair of coding sequences. RNA has an important coding function in protein synthesis, and yet the consequences of RNA oxidation are largely unknown. Some non-coding nucleic acid is functional, e.g. promoters, and damage to these sequences may well have biological consequences. Similarly, oxidative damage to DNA may promote microsatellite instability, inhibit methylation and accelerate telomere shortening. DNA repair appears pivotal to the maintenance of genome integrity, and genetic alterations in repair capacity, due to single nucleotide polymorphisms or mutation, may account for inter-individual differences in cancer susceptibility. This review will survey these aspects of oxidative damage to nucleic acids and their implication for disease. 相似文献
993.
Veerareddy S Cooke CL Baker PN Davidge ST 《American journal of physiology. Heart and circulatory physiology》2004,287(1):H40-H45
Oxidative stress mediated by prooxidants has been implicated in the pathogenesis of vascular disorders. However, the effect of prooxidants on myogenic regulation of vascular function and the differential influence of gender is not known. SOD, an intracellular enzyme, restricts excess prooxidant levels and may limit vascular dysfunction. We therefore tested the effects of Cu,Zn SOD deficiency on vascular tone in both male and female SOD knockout (SOD-/-) mice. We hypothesized that myogenic tone would be enhanced in SOD-/- mice by excess prooxidants compared with wild-type control mice. Indeed, resistance-sized mesenteric arteries from SOD-/- mice exhibited enhanced myogenic tone compared with control mice. Myogenic tone was lower in female than male control mice. Interestingly, this gender effect was absent in SOD-/- mice, such that myogenic tone of mesenteric arteries from females was equated to that of arteries from males. Furthermore, the pathways that modulate myogenic tone were diverse. In both male and female control mice, inhibition of prostaglandin H synthase (PGHS) and nitric oxide synthase (NOS) pathways enhanced myogenic tone. In female SOD-/- mice, inhibition of PGHS and NOS pathways enhanced myogenic tone to a greater extent compared with control mice. Conversely, in male SOD-/- mice, NOS and PGHS inhibition did not alter tone and only inhibition of gap junctions enhanced myogenic tone. In conclusion, this study revealed enhanced myogenic tone in SOD-/- mice compared with control mice. Furthermore, Cu,Zn SOD deficiency particularly enhanced myogenic tone in female mice such that their vascular tone attained the level of male SOD-/- mice, possibly mediated by prooxidants. 相似文献
994.
995.
This review focuses on the effect of gonadal steroid hormones, androgen and estrogen, on dendrites in the adult rat central nervous system (CNS). Four hormone-responsive nuclei are considered: The spinal nucleus of the bulbocavernosus (SNB), the medial nucleus of the amygdala (MeA), the ventromedial nucleus of the hypothalamus (VMN), and the CA1 region of the dorsal hippocampus. Particular emphasis is placed on the mode of hormone action in each nucleus. In the SNB, VMN, and hippocampus, hormones appear to mediate their effects indirectly, via cells other than those that display morphological plasticity. In the MeA, estrogen and/or androgen appears to act primarily on those cells whose dendrites are modulated by the hormone. Importantly, increasing levels of gonadal hormones do not simply result in increases in dendritic parameters. In the VMN, high levels of estrogen associated with proestrus increase dendritic spine density in one subset of cells and reduce spine density in another subset. The pyramidal cells of dorsal CA1 also undergo phasic changes in dendritic spine and synapse density across the estrous cycle. The estrogen-induced excitatory synapses connect with preexisting axonal boutons that also form synapses with other CA1 cells, thereby increasing the divergence of excitatory afferents to dorsal CA1. These findings indicate that gonadal steroids have a profound impact on the morphology of dendrites and patterns of synaptic connectivity. Consequently, the experimental manipulation of hormone levels is a powerful tool to study structure-function relationships in the mammalian brain. 相似文献
996.
Joshua A. Prado Helena Puszka Alexander Forman Benjamin Cooke James A. Fitzsimons 《Ecological Management & Restoration》2018,19(2):136-146
The Land for Wildlife program started in Victoria in 1981 as a voluntary program with the broad aim of supporting landholders in providing habitat for wildlife on their property. The program has since spread across Australia and is implemented in a range of guises, through a variety of governance approaches. This research collected qualitative and quantitative data on Land for Wildlife programs across Australia to conduct the first national review. Data were gathered on changes in program membership to assess different participation trends. In addition, phone interviews with Land for Wildlife coordinators throughout Australia were conducted to explore how the programs are positioned in delivering biodiversity outcomes in a range of different regions. Over 14,000 properties covering 2.3 million ha are currently registered under Land for Wildlife programs. with at least 500,000 ha of habitat managed for conservation. Limited resources present a large challenge faced by a number of programs, with generally low funding and staffing resulting in restricted biodiversity focus and conservation outcomes. We suggest options to enhance the programs and propose future research directions. 相似文献
997.
998.
Of 77 married women with Crohn''s disease, 25 were sterile. In the remaining 52 (98 pregnancies) the risks of prematurity, stillbirth, abortion, or congenital abnormality were not increased. There was no evidence that pregnancy exerted adverse effects on the course of the disease or increased the mortality rate. Sterility was the main problem encountered. 相似文献
999.
1000.
W. E. Cooke 《BMJ (Clinical research ed.)》1930,1(3609):433-437