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121.
Over a period of 20 years, Chinese privet, Ligustrum sinense, invaded a mixed hardwood forest in western North Carolina, USA. The invasion penetrated about 30m under the canopy trees, providing 100% cover of the forest floor. Under the privets and in a nearby privet-poor reference area we marked off twenty, one square meter plots with string. All plants in each square meter of both areas were tallied in the spring of 1999 and young trees less than 1m high were again counted in September. We removed privets of the invaded area in November and again tallied all plants in both areas the following spring of 2000. In the spring of 1999, the mean number of herb species per square meter under the privet was 41%, and stem counts 75% less than in the reference area. 42% of herb species found in the reference area were missing under the privet. After removing the privets in the fall of 1999, the number of both native species and stems increased in the privet area the following spring. Plots of density of two native plants against privet density showed both native plants decreasing under increasing privet cover. In the spring of 1999, there were 4 species and 274 stems of tree seedlings in the privet area. In September of that year, we found only one small American holly tree, a highly shade-tolerant species, remaining under the privet. Our data support the thesis that Chinese privet can severely reduce herbaceous species and almost completely suppress tree regeneration in a mixed hardwood forest. 相似文献
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Pituitary adenylate cyclase-activating polypeptide (PACAP) peptides, which are co-localized with acetylcholine in preganglionic parasympathetic fibers innervating guinea pig intracardiac ganglia, depolarize and increase excitability of intracardiac neurons. Perforated patch whole cell recordings were used to test whether PACAP27-enhanced activation of Ih contributed to the increase in excitability. In current clamp, 100 nM PACAP27 increased rectification during 500-ms hyperpolarizations and increased the number of anodal break action potentials (APs). PACAP27 also increased the number of APs produced by 500-ms depolarizing currents. In voltage clamp, the effects of 100 nM PACAP27 were determined during hyperpolarizing steps from -50 mV to voltages between -60 and -120 mV. PACAP27 increased the amplitude and rate of activation of Ih. PACAP27 shifted the voltage dependence of activation of Ih by 6.6 mV. The effect of PACAP27 was eliminated by pretreatment with the Ih inhibitor ZD7288 (100 microM). The adenylyl cyclase activator forskolin (10 microM) produced a similar shift in the voltage dependence of Ih activation. We conclude that PACAP27 enhances Ih by shifting the voltage dependence of activation and propose that this effect is mediated primarily by PAC1 receptor activation of adenylyl cyclase and generation of cAMP. Furthermore, we propose that the peptide-enhanced Ih contributes to the PACAP27-induced increase in membrane excitability. 相似文献
124.
Choi EK Zaidi NF Miller JS Crowley AC Merriam DE Lilliehook C Buxbaum JD Wasco W 《The Journal of biological chemistry》2001,276(22):19197-19204
Calsenilin is a member of the recoverin family of neuronal calcium-binding proteins that we have previously shown to interact with presenilin 1 (PS1) and presenilin 2 (PS2) holoproteins. The expression of calsenilin can regulate the levels of a proteolytic product of PS2 (Buxbaum, J. D., Choi, E. K., Luo, Y., Lilliehook, C., Crowley, A. C., Merriam, D. E., and Wasco, W. (1998) Nat. Med. 4, 1177-1181) and reverse the presenilin-mediated enhancement of calcium signaling (Leissring, M. A., Yamasaki, T. R., Wasco, W., Buxbaum, J. D., Parker, I., and LaFerla, F. M. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 8590-8593). Here, we have used cultured mammalian cells that transiently or stably express calsenilin to extend the characterization of calsenilin and of the calsenilin-PS2 interaction. We have found that calsenilin has the ability to interact with endogenous 25-kDa C-terminal fragment (CTF) that is a product of regulated endoproteolytic cleavage of PS2 and that the presence of the N141I PS2 mutation does not significantly alter the interaction of calsenilin with PS2. Interestingly, when the 25-kDa PS2 CTF and the 20-kDa PS2 CTF are both present, calsenilin preferentially interacts with the 20-kDa CTF. Increases in the 20-kDa fragment are associated with the presence of familial Alzheimer's disease-associated mutations (Kim, T., Pettingell, W. H., Jung, Y., Kovacs, D. M., and Tanzi, R. E. (1997) Science 277, 373-376). However, the finding that the production of the 20-kDa fragment is regulated by the phosphorylation of PS2 (Walter, J., Schindzielorz, A., Grunberg, J., and Haass, C. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 1391-1396) suggests that it is a regulated physiological event that also occurs in the absence of the familial Alzheimer's disease-associated mutations in PS2. Finally, we have demonstrated that calsenilin is a substrate for caspase-3, and we have used site-directed mutagenesis to map the caspase-3 cleavage site to a region that is proximal to the calcium binding domain of calsenilin. 相似文献
125.
N. Maritza Dowling Carey E. Gleason JoAnn E. Manson Howard N. Hodis Virginia M. Miller Eliot A. Brinton Genevieve Neal-Perry M. Nanette Santoro Marcelle Cedars Rogerio Lobo George R. Merriam Whitney Wharton Frederick Naftolin Hugh Taylor S. Mitchell Harman Sanjay Asthana 《PloS one》2013,8(7)
Objectives
While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables.Methods
A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ε4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification.Results
The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were “low-risk” and 38% “high-risk”. Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-ε4 was higher in the high-risk class compared with rates in the low-risk class.Conclusion
Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could in turn clarify preclinical disease, and screening and preventive strategies.ClinicalTrials.gov NCT00154180相似文献126.
Chang Yu Jun Yu Xiaotian Yao William KK Wu Youyong Lu Senwei Tang Xiangchun Li Li Bao Xiaoxing Li Yong Hou Renhua Wu Min Jian Ruoyan Chen Fan Zhang Lixia Xu Fan Fan Jun He Qiaoyi Liang Hongyi Wang Xueda Hu Minghui He Xiang Zhang Hancheng Zheng Qibin Li Hanjie Wu Yan Chen Xu Yang Shida Zhu Xun Xu Huanming Yang Jian Wang Xiuqing Zhang Joseph JY Sung Yingrui Li Jun Wang 《Cell research》2014,24(6):701-712
Single-cell sequencing is a powerful tool for delineating clonal relationship and identifying key driver genes for personalized cancer management. Here we performed single-cell sequencing analysis of a case of colon cancer. Population genetics analyses identified two independent clones in tumor cell population. The major tumor clone harbored APC and TP53 mutations as early oncogenic events, whereas the minor clone contained preponderant CDC27 and PABPC1 mutations. The absence of APC and TP53 mutations in the minor clone supports that these two clones were derived from two cellular origins. Examination of somatic mutation allele frequency spectra of additional 21 whole-tissue exome-sequenced cases revealed the heterogeneity of clonal origins in colon cancer. Next, we identified a mutated gene SLC12A5 that showed a high frequency of mutation at the single-cell level but exhibited low prevalence at the population level. Functional characterization of mutant SLC12A5 revealed its potential oncogenic effect in colon cancer. Our study provides the first exome-wide evidence at single-cell level supporting that colon cancer could be of a biclonal origin, and suggests that low-prevalence mutations in a cohort may also play important protumorigenic roles at the individual level. 相似文献
127.
Drosophila melanogaster is sensitive to a variety of psychotropic and neurotropic drugs that alter neurotransmitter metabolism in humans. For many drugs the activity is a function of the stage of development of the organism. An example is the convulsant allylglycine (2-amino 4-pentenoic acid). Larvae were unaffected by a dose of allylglycine that was lethal for adults. Larvae that had been exposed to the drug continuously through three instars were able to pupate. In the pupae, which were no longer exposed to the drug, the pharate adults appeared to mature normally but subsequently died, usually before emerging from the puparium case. Allylglycine is known to inhibit mammalian glutamate decarboxylase. This enzyme is present in homogenates of Drosophila. Larvae possess a much smaller amount of glutamate decarboxylase than do adults. Allylglycine has a minimal effect on glutamate decarboxylase in vivo or in vitro. Several drug-resistant strains have been isolated. 相似文献
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130.
B. Phillips A. N. Billin C. Cadwell R. Buchholz C. Erickson J. R. Merriam J. Carbon S. J. Poole 《Molecular genetics and genomics : MGG》1998,260(1):20-29
The Cbf5 protein of Saccharomyces cerevisiae was originally identified as a low-affinity centromeric DNA-binding protein, and cbf5 mutants have a defect in rRNA synthesis. A closely related protein from mammals, NAP57, is a nucleolar protein that coimmunoprecipitates with the nucleolar phosphoprotein Nopp140. To study the function of this protein family in a higher eukaryote that is amenable to genetic approaches, the gene encoding a Drosophilamelanogaster homolog, Nop60B, was identified. The predicted Drosophila protein shares a high degree of sequence identity over a 380-residue region with both the mammalian and yeast proteins, and shares several conserved motifs with the prokaryotic tRNA pseudouridine 55 synthases. Nop60B RNA is found at high levels in nurse cells and in the oocyte, and is present throughout development. Nop60B protein is localized primarily to the nucleolus of interphase cells, and is absent from the chromosomes during mitosis. Nop60B mutants were generated and shown to be homozygous lethal. The Drosophila gene can rescue the lethal phenotype of yeast cbf5 mutations, showing that the function of this protein has been conserved from yeast to Drosophila. 相似文献