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81.
Sabeti PC Reich DE Higgins JM Levine HZ Richter DJ Schaffner SF Gabriel SB Platko JV Patterson NJ McDonald GJ Ackerman HC Campbell SJ Altshuler D Cooper R Kwiatkowski D Ward R Lander ES 《Nature》2002,419(6909):832-837
The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection. 相似文献
82.
A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes 总被引:12,自引:0,他引:12
A repetitive DNA sequence has been identified in the Drosophila melanogaster genome that appears to be localized specifically within genes of the bithorax and Antennapedia complexes that are required for correct segmental development. Initially identified in cloned copies of the genes Antennapedia, Ultrabithorax and fushi tarazu, the sequence is also contained within two other DNA clones that have characteristics strongly suggesting that they derive from other homoeotic genes. 相似文献
83.
E. Seifter G. Rettura M. Zisblatt S. M. Levenson N. Levine A. Davidson J. Seifter 《Cellular and molecular life sciences : CMLS》1973,29(11):1379-1382
Riassunto L'applicazione di un parziale bendaggio nei topi produce uno stato di fisiologica tensione caratterizzata, in parte, dall'involuzione della ghiandola del timo. Topi sottoposti a una tale tensione sono più suscettibili allo sviluppo dei tumori quando vengono inoculati con un oncogenico virus. 相似文献
84.
85.
Many transformed cells in culture have been found to express elevated levels of a cellular tumour antigen, termed p53. This protein has also been implicated in the regulation of cellular growth. For these reasons experiments were designed to examine the expression of p53 as quiescent cultures of nontransformed 3T3 fibroblasts were stimulated to reenter the cell cycle. Synchronous populations of cells were obtained by releasing a culture from density-dependent inhibition of growth with the addition of fresh serum. Steady-state levels of p53 protein and mRNA were measured as a function of time after addition of serum to quiescent cultures and the rate of synthesis of p53 protein was analysed at a number of time points. The results, reported here, demonstrate an increase in the synthesis and steady-state levels of p53 protein and mRNA prior to DNA synthesis in late G1, and suggest a role for p53 in the progression of cells from a growth-arrested state to an actively dividing state. 相似文献
86.
L W Kitchen F Barin J L Sullivan M F McLane D B Brettler P H Levine M Essex 《Nature》1984,312(5992):367-369
Human T-cell leukaemia virus type III (HTLV-III) is suspected of having a key role in the pathogenesis of acquired immune deficiency syndrome (AIDS). Epidemiological data suggest that AIDS is transmitted by an infectious agent through intimate contact with body secretions, blood or blood products. To maintain haemostasis, many haemophiliac patients depend on commercially prepared clotting concentrates made from large multi-donor plasma pools and are thus at increased risk of developing the disease. We report here that, using indirect membrane immunofluorescence and radioimmunoprecipitation with SDS-polyacrylamide gel electrophoresis, we have detected antibodies to HTLV-III in 30 of 47 (64%) asymptomatic haemophiliacs and in all of three haemophiliacs who either had or soon developed AIDS. Of 34 samples drawn before 1984, 18 (53%) were antibody-positive, whereas of 16 samples drawn during 1984, 15 (94%) were positive (P less than or equal to 0.002). These data suggest that exposure to HTLV-III antigens is widespread among asymptomatic haemophiliacs. 相似文献
87.
Demethylation of CpG islands in embryonic cells 总被引:16,自引:0,他引:16
DNA in differentiated somatic cells has a fixed pattern of methylation, which is faithfully copied after replication. By contrast, the methylation patterns of many tissue-specific and some housekeeping genes are altered during normal development. This modification of DNA methylation in the embryo has also been observed in transgenic mice and in transfection experiments. Here we report the fate in mice of an in vitro-methylated adenine phosphoribosyltransferase transgene. The entire 5' CpG island region became demethylated, whereas the 3' end of the gene remained modified and was even methylated de novo at additional sites. Transfection experiments in vitro show that the demethylation is rapid, is specific for embryonic cell-types and affects a variety of different CpG island sequences. This suggests that gene sequences can be recognized in the early embryo and imprinted with the correct methylation pattern through a combination of demethylation and de novo methylation. 相似文献
88.
89.
Functions of the MDM2 oncoprotein 总被引:34,自引:1,他引:33
90.
Autophagy fights disease through cellular self-digestion 总被引:3,自引:0,他引:3
Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health. 相似文献