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121.
Huang S Shu L Dilling MB Easton J Harwood FC Ichijo H Houghton PJ 《Molecular cell》2003,11(6):1491-1501
Under serum-free conditions, rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), induces apoptosis of cells lacking functional p53. Cells expressing wild-type p53 or p21(Cip1)arrest in G1 and remain viable. In cells lacking functional p53, rapamycin or amino acid deprivation induces rapid and sustained activation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase, and elevation of phosphorylated c-Jun that results in apoptosis. This stress response depends on expression of eukaryotic initiation factor 4E binding protein 1 and is suppressed by p21(Cip1) independent of cell cycle arrest. Rapamycin induces p21(Cip1) binding to ASK1, suppressing kinase activity and attenuating cellular stress. These results suggest that inhibition of mTOR triggers a potentially lethal response that is prevented only in cells expressing p21(Cip1). 相似文献
122.
Hambright K. David; Zohary Tamar; Easton James; Azoulay Bonnie; Fishbein Tatiana 《Journal of plankton research》2001,23(2):165-174
A bloom of the filamentous, N2-fixing cyanobacterium Aphanizomenonovalisporum Forti occurred for the first time in Lake Kinneretduring late summer and fall 1994. During subsequent years (19951999),Aphanizomenon also appeared in late summer and fall, but didnot bloom. In outdoor microcosm experiments, we examined zooplanktongrazing on Lake Kinneret phytoplankton, with and without Aphanizomenonpresent, and the effects of N, P and N:P ratios on phytoplanktongrowth. In one-day feeding experiments, clearance and grazingrates of the ambient Lake Kinneret zooplankton assemblage feedingin lake water dominated by Aphanizomenon were 10-fold lowerthan in water without Aphanizomenon. We suspect that the lowgrazing rates were due to interference caused by the presenceof Aphanizomenon. In 9-day nutrient addition experiments, significantenhancement effects on phytoplankton were detected with additionsof either P or N; a high N:P was better for phytoplankton growththan a low N:P. After 7 days, bottles receiving low P and noN additions were dominated by Oscillatoria sp. and Closteriumacutum; few Aphanizomenon were present. In contrast, bottlesreceiving high P and N additions had large increases of Aphanizomenon,as well as Oscillatoria and Closterium. There was a tendencyfor more green algae and diatoms with increasing N additions.These results provide evidence that (i) non-grazeability ofAphanizomenon enabled it to gain a competitive advantage overgrazeable phytoplankton, and (ii) that nutrient limitation,but not grazing, was probably important in the eventual declineof the Aphanizomenon bloom. 相似文献
123.
Linkage analysis of chromosome 1q markers in 136 prostate cancer families. The Cancer Research Campaign/British Prostate Group U.K. Familial Prostate Cancer Study Collaborators. 总被引:2,自引:0,他引:2
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R A Eeles F Durocher S Edwards D Teare M Badzioch R Hamoudi S Gill P Biggs D Dearnaley A Ardern-Jones A Dowe R Shearer D L McLennan R L Norman P Ghadirian A Aprikian D Ford C Amos T M King F Labrie J Simard S A Narod D Easton W D Foulkes 《American journal of human genetics》1998,62(3):653-658
Prostate cancer shows evidence of familial aggregation, particularly at young ages at diagnosis, but the inherited basis of familial prostate cancer is poorly understood. Smith et al. recently found evidence of linkage to markers on 1q, at a locus designated "HPC1," in 91 families with multiple cases of early-onset prostate cancer. Using both parametric and nonparametric methods, we attempted to confirm this finding, in 60 affected related pairs and in 76 families with three or more cases of prostate cancer, but we found no significant evidence of linkage. The estimated proportion of linked families, under a standard autosomal dominant model, was 4%, with an upper 95% confidence limit of 31%. We conclude that the HPC1 locus is responsible for only a minority of familial prostate cancer cases and that it is likely to be most important in families with at least four cases of the disease. 相似文献
124.
Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. 总被引:39,自引:0,他引:39
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D Ford D F Easton M Stratton S Narod D Goldgar P Devilee D T Bishop B Weber G Lenoir J Chang-Claude H Sobol M D Teare J Struewing A Arason S Scherneck J Peto T R Rebbeck P Tonin S Neuhausen R Barkardottir J Eyfjord H Lynch B A Ponder S A Gayther M Zelada-Hedman et al. 《American journal of human genetics》1998,62(3):676-689
The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age. 相似文献
125.
Genetic heterogeneity and localization of a familial breast-ovarian cancer gene on chromosome 17q12-q21. 总被引:8,自引:6,他引:2
S A Smith D F Easton D Ford J Peto K Anderson D Averill M Stratton M Ponder C Pye B A Ponder 《American journal of human genetics》1993,52(4):767-776
In a study of 31 breast cancer families and 12 breast-ovarian cancer families, we have obtained clear evidence of linkage to markers on chromosome 17q in the families with ovarian cancer (maximum lod score 3.34 at theta = .04) but only weak evidence in those without ovarian cancer. Recombinant events indicate that the gene lies between D17S588 and D17S250. 相似文献
126.
Takeyoshi Miki Alan M. Easton Robert H. Rownd 《Molecular & general genetics : MGG》1978,158(3):217-224
Summary The drug resistance genes on the r-determinants component of the composite R plasmid NR1 were mapped on the EcoRI restriction endonuclease fragments of the R plasmid by cloning the fragments using the plasmid RSF2124 as a vector. The sulfonamide (Su) and streptomycin/spectinomycin (Sm/Sp) resistance genes are located on EcoRI fragment G of NR1. The expression of resistance to mercuric ions (Mer) requires both EcoRI fragment H and I of NR1. The expression of chloramphenicol (Cm) and fusidic acid (Fus) resistance requires EcoRI fragments A and J of NR1. The kan fragment of the related R plasmid R6-5 can substitute for EcoRI fragment J of NR1 in the expression of Cm and Fus resistance. The structural genes for Cm and Fus resistance appear to be a part of an operon whose expression is controlled by the same promoter. 相似文献
127.
Plasminogen activator in chick embryo muscle cells: induction of enzyme by RSV, PMA and retinoic acid. 总被引:13,自引:0,他引:13
To explore the generality of the effects of sarcoma viruses, tumor-promoting phorbol esters and retinoic acid, we have studied plasminogen activator production in differentiating chick myogenic cultures. Although slightly higher than in chick fibroblast cultures, the level of spontaneously synthesized enzyme is low; it reaches a peak shortly after maximum cell fusion has been completed and then declines. Rous sarcoma virus (RSV) transformation of differentiating myotubes was accomplished by infecting myoblasts with a temperature-sensitive mutant, maintaining cultures at the nonpermissive temperature until completion of fusion and shifting to permissive temperatures at selected times thereafter. RSV transformation, phorbol myristate acetate (PMA) and retinoic acid all induced high levels of plasminogen activator production by differentiating myotubes in the absence of DNA synthesis. In comparison with fibroblasts, virus-induced enzyme synthesis by myogenic cultures proceeded more slowly but ultimately reached comparably high levels. Whereas cAMP strongly repressed RSV- and PMA-induced plasminogen activator production by chick fibroblasts, it weakly stimulated enzyme synthesis by myotubes. This suggests that enzyme induction by RSV and PMA is not mediated primarily through effects on cAMP metabolism. 相似文献
128.
Acrosin was detected by immunofluorescence in the spermatozoan acrosomes of artiodactyla (bull, ram and boar), perissodactyla (horse), carnivora (dog and cat), lagomorpha (rabbit) and primates (human) using anti-bovine acrosin immunoglobulins. The results indicate that the acrosin molecules of several mammalian species possess antigenic similarities. 相似文献
129.
130.
SalI restriction endonuclease maps of FII incompatibility group R plasmids NR1, NR84, and R6 have been determined by sequential digestion of plasmid DNA with EcoRI and SalI and subsequent analysis of the fragments by electrophoresis on agarose gels. In the composite R plasmid NR1 there are five SalI sites, one in the r-determinants component and four in the RTF-Tc component. SalI cleavage of transitioned NR1 DNA, which contains tandem sequences of the r-determinants in a head-to-tail orientation, produces the five original bands plus a single new amplified band whose mobility on agarose gels corresponds to the monomer r-determinants DNA. NR84 has a total of four SalI sites. It is missing one of the SalI sites near the repA locus. R6 has five SalI sites, four the same as those of NR84, and one additional site within the Km transposon Tn601. 相似文献