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61.
Monkey (Mk) CD9 antigen has been shown previously to increase the diphtheria toxin (DT) sensitivity of cells when co-expressed with Mk proHB-EGF (DT receptor). We have elucidated here the mechanism whereby Mk CD9 influences Mk proHB-EGF and present evidence that Mk CD9 is a coreceptor for DT. We observed that Mk CD9 not only increased the DT sensitivity but also increased the DT receptor affinity of cells. Furthermore, the higher the Mk CD9/Mk proHB-EGF ratio, the higher the affinity. In contrast, mouse (Ms) CD9 did not increase the toxin sensitivity or receptor affinity of cells when co-expressed with Mk proHB-EGF. Using Mk/Ms chimeric CD9 molecules, we determined that the second extracellular domain of Mk CD9 is responsible for both increased sensitivity and receptor affinity. This domain of Mk CD9 also interacts with Mk proHB-EGF in a yeast two-hybrid system. Our findings thus suggest that Mk CD9 has a direct physical interaction with Mk proHB-EGF to form a DT receptor complex and that this contact may change the conformation of the receptor to increase DT binding affinity and consequently increase toxin sensitivity. We thus propose that Mk CD9 is a coreceptor for DT. 相似文献
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63.
Cloning and Characterization of the Pseudomonas aeruginosa zwf Gene Encoding Glucose-6-Phosphate Dehydrogenase, an Enzyme Important in Resistance to Methyl Viologen (Paraquat) 总被引:1,自引:0,他引:1 下载免费PDF全文
Ju-Fang Ma Paul W. Hager Michael L. Howell Paul V. Phibbs Daniel J. Hassett 《Journal of bacteriology》1998,180(7):1741-1749
64.
M. de L. Brooke N. B. Davies D. G. Noble 《Proceedings. Biological sciences / The Royal Society》1998,265(1403):1277-1282
On Wicken Fen and nearby watercourses eastern England, parasitism by cuckoos, Cuculus canorus, declined from 26% and 16% of reed warbler (Acrocephalus scirpaceus) nests in 1985 and 1986, respectively, to 2 to 6% of nests in 1995 to 1997, owing to a decline in cuckoos. Experiments with model eggs showed that over this 12-year period there was a marked decline in host rejection of non-mimetic eggs, from rejection at 75% of reed warbler nests in 1985 to 1986 to 25%, nests in 1997. Calculations suggest that this decline in host defences is too rapid to reflect only genetic change, and is more likely to be the outcome of adaptive phenotypic flexibility. Two other results show flexibility in host responses. First, there was a seasonal decline in rejection, which accompanied the seasonal decline in parasitism. Second, although rejection did not vary with proximity to a naturally parasitized nest within the 3.4km2 of Wicken Fen and its surrounds, there was no rejection at a small unparasitized population 11km away. Flexible host defences will be advantageous when there are costs of rejection as well as short-term temporal changes and small-scale geographical variation in parasitism rate. Other recent studies reporting changes in host defences may also reflect phenotypic flexibility rather than evolutionary change. 相似文献
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Alexandra Mangili Julian Falutz Jean-Claude Mamputu Miganush Stepanians Brooke Hayward 《PloS one》2015,10(10)
BackgroundTesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy.Objectives1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin.MethodsData were analyzed from two Phase 3 studies in which HIV-infected patients with excess abdominal fat were randomized in a 2:1 ratio to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) subcutaneously daily for 6 months, using ANOVA and ANCOVA models.ResultsMetabolic syndrome (MetS-IDF or MetS-NCEP) and FRS were significantly associated with VAT at baseline. Presence of metabolic syndrome ([MetS-NCEP), triglyceride levels >1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively). No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm2 for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI) and baseline VAT (95% confidence interval [CI] 2.03; 7.44).ConclusionsIndividuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm2 was 3.9 times greater for tesamorelin-treated patients than that of patients receiving placebo. 相似文献
67.
Richard Lu Bobby Brooke Herrera Heather D. Eshleman Yang Fu Alexander Bloom Zhigang Li David B. Sacks Marcia B. Goldberg 《PLoS pathogens》2015,11(10)
The intracellular bacterial pathogen Shigella infects and spreads through the human intestinal epithelium. Effector proteins delivered by Shigella into cells promote infection by modulating diverse host functions. We demonstrate that the effector protein OspB interacts directly with the scaffolding protein IQGAP1, and that the absence of either OspB or IQGAP1 during infection leads to larger areas of S. flexneri spread through cell monolayers. We show that the effect on the area of bacterial spread is due to OspB triggering increased cell proliferation at the periphery of infected foci, thereby replacing some of the cells that die within infected foci and restricting the area of bacterial spread. We demonstrate that OspB enhancement of cell proliferation results from activation of mTORC1, a master regulator of cell growth, and is blocked by the mTORC1-specific inhibitor rapamycin. OspB activation of mTORC1, and its effects on cell proliferation and bacterial spread, depends on IQGAP1. Our results identify OspB as a regulator of mTORC1 and mTORC1-dependent cell proliferation early during S. flexneri infection and establish a role for IQGAP1 in mTORC1 signaling. They also raise the possibility that IQGAP1 serves as a scaffold for the assembly of an OspB-mTORC1 signaling complex. 相似文献
68.
Brooke Sadler Gabe Haller Howard Edenberg Jay Tischfield Andy Brooks John Kramer Marc Schuckit John Nurnberger Alison Goate 《PloS one》2015,10(8)
Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima’s D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies. 相似文献
69.
Brooke Soden Micaela E. Christopher Jacqueline Hulslander Richard K. Olson Laurie Cutting Janice M. Keenan Lee A. Thompson Sally J. Wadsworth Erik G. Willcutt Stephen A. Petrill 《PloS one》2015,10(1)
Reading comprehension is a foundational academic skill and significant attention has focused on reading development. This report is the first to examine the stability and change in genetic and environmental influences on reading comprehension across Grades 1 to 6. This developmental range is particularly important because it encompasses the timespan in which most children move from learning how to read to using reading for learning. Longitudinal simplex models were fitted separately for two independent twin samples (N = 706; N = 976). Results suggested that the shared environment contributed to variance in early but not later reading. Instead, stability in reading development was largely mediated by continuous genetic influences. Thus, although reading is clearly a learned skill and the environment remains important for reading development, individual differences in reading comprehension appear to be also influenced by a core of genetic stability that persists through the developmental course of reading. 相似文献
70.
Benjamin F. Mentiplay Luke G. Perraton Kelly J. Bower Brooke Adair Yong-Hao Pua Gavin P. Williams Rebekah McGaw Ross A. Clark 《PloS one》2015,10(10)