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排序方式: 共有114条查询结果,搜索用时 31 毫秒
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A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews. 总被引:7,自引:2,他引:5
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V Meiner D Landsberger N Berkman A Reshef P Segal H C Seftel D R van der Westhuyzen M S Jeenah G A Coetzee E Leitersdorf 《American journal of human genetics》1991,49(2):443-449
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density-lipoprotein (LDL) receptor. Here we characterize an LDL-receptor founder mutation that is associated with a distinct LDL-receptor haplotype and is responsible for FH in 35% of 71 Jewish-Ashkenazi FH families in Israel. Sixty four percent (16/25) of the Ashkenazi patients who carry this mutant allele were of Lithuanian origin. The mutation was not found in 47 non-Ashkenazi FH families. This mutation was prevalent (8/10 FH cases) in the Jewish community in South Africa, which originated mainly from Lithuania. The mutation, a 3-bp in-frame deletion that would result in the elimination of Gly197, has been previously designated FH-Piscataway. PCR amplification of a DNA fragment that includes the mutation in heterozygous individuals results in the formation of a heteroduplex that can be demonstrated by PAGE and used for molecular diagnosis. 相似文献
5.
W. J. Keon P. Bédard Y. Akyurekli M. Brais F. Berkman K. W. Tan B. C. Morton 《CMAJ》1976,114(4):312-315
During a 5-year period (Apr. 14, 1970 to Apr. 14, 1975) 930 patients underwent aortocoronary bypass grafting; the procedure was done as an emergency in 141. Of the entire group 3.3% died at operation, 1.6% died in hospital and 5.8% died later; of the patients undergoing emergency grafting 12.1% died at operation and 5.7% died later. From a detailed analysis of the first 600 patients it was found that both operative and late mortality were clearly related to two factors: severe left ventricular dysfunction at the time of operation and inadequate surgical treatment because of insertion of insufficient numbers of grafts or because of poor blood flow through the grafts. 相似文献
6.
S. J. Oyler-McCance F. A. Ransler L. K. Berkman T. W. Quinn 《Conservation Genetics》2007,8(6):1339-1353
For management purposes, the range of naturally occurring trumpeter swans (Cygnus buccinator) has been divided into two populations, the Pacific Coast Population (PP) and the Rocky Mountain Population (RMP). Little
is known about the distribution of genetic variation across the species’ range despite increasing pressure to make difficult
management decisions regarding the two populations and flocks within them. To address this issue, we used rapidly evolving
genetic markers (mitochondrial DNA sequence and 17 nuclear microsatellite loci) to elucidate the underlying genetic structure
of the species. Data from both markers revealed a significant difference between the PP and RMP with the Yukon Territory as
a likely area of overlap. Additionally, we found that the two populations have somewhat similar levels of genetic diversity
(PP is slightly higher) suggesting that the PP underwent a population bottleneck similar to a well-documented one in the RMP.
Both genetic structure and diversity results reveal that the Tri-State flock, a suspected unique, non-migratory flock, is
not genetically different from the Canadian flock of the RMP and need not be treated as a unique population from a genetic
standpoint. Finally, trumpeter swans appear to have much lower mitochondrial DNA variability than other waterfowl studied
thus far which may suggest a previous, species-wide bottleneck. 相似文献
7.
Thomas A Glass Carlos Mendes de Leon Richard A Marottoli Lisa F Berkman 《BMJ (Clinical research ed.)》1999,319(7208):478-483
ObjectivesTo examine any association between social, productive, and physical activity and 13 year survival in older people. DesignProspective cohort study with annual mortality follow up. Activity and other measures were assessed by structured interviews at baseline in the participants’ homes. Proportional hazards models were used to model survival from time of initial interview.SettingCity of New Haven, Connecticut, United States.Participants2761 men and women from a random population sample of 2812 people aged 65 and older.ResultsAll three types of activity were independently associated with survival after age, sex, race/ethnicity, marital status, income, body mass index, smoking, functional disability, and history of cancer, diabetes, stroke, and myocardial infarction were controlled for.ConclusionsSocial and productive activities that involve little or no enhancement of fitness lower the risk of all cause mortality as much as fitness activities do. This suggests that in addition to increased cardiopulmonary fitness, activity may confer survival benefits through psychosocial pathways. Social and productive activities that require less physical exertion may complement exercise programmes and may constitute alternative interventions for frail elderly people.
Key messages
- Little is known about predictors of survival among elderly people
- Physical activity is clearly good for health, but the potential benefits of social activities have not been studied
- Social and productive activities are as effective as fitness activities in lowering the risk of death
- Enhanced social activities may help to increase the quality and length of life
8.
Mallari JP Choy CJ Hu Y Martinez AR Hosaka M Toriyabe Y Maung J Blecha JE Pavkovic SF Berkman CE 《Bioorganic & medicinal chemistry》2004,12(22):6011-6020
A series of alkyl and aryl phosphonyl, thiophosphonyl, and dithiophosphonyl derivatives of (S)- and (R)-glutamic acid were prepared and examined for inhibitory potency against glutamate carboxypeptidase (carboxypeptidase G). The acquisition of the phosphonamidodithioic acids and the individual phosphonamidothioic acid diastereomers was achieved through a common phosphonamidothiolate precursor, which also allowed for the chromatographic resolution of the chiral phosphorus center of the phosphonamidothioic acids. The most potent inhibitor of the series was the n-butylphosphonamidate derivative of the natural isomer of glutamic acid. Although each diastereomeric pair of three phosphonamidothionates exhibited stereoselective inhibition consistent with the configuration of the chiral phosphorus center, this effect was generally not remarkable. More important, was the effect of carbon stereochemistry upon glutamate carboxypeptidase inhibition as exemplified by a limited series of enantiomeric pairs of phosphonamidate and phosphonamidodithionate derivatives of glutamic acid. The phosphonamidate analogs derived from the unnatural stereoisomer of glutamic acid were devoid of inhibitory potency in contrast to their enantiomers. Surprisingly, the phosphonamidodithionates derived from the unnatural stereoisomer of glutamic acid demonstrated greater inhibitory potency than their naturally-derived antipodes. 相似文献
9.
Rodriguez CE Lu H Martinez AR Hu Y Brunelle A Berkman CE 《Journal of enzyme inhibition》2001,16(4):359-365
A limited series of N-thiophosphonyl-glutamates were found to be inhibitors of the prostate-specific membrane antigen (PSMA) form of glutamate carboxypeptidase II. Comparative inhibitory profiles of an analogous O-thiophosphonyl-2-hydroxyglutarate revealed that the amido-linkage of the N-thiophosphonyl-glutamate provides a significant enhancement of inhibitory potency presumably due to significant hydrogen-bonding interactions with acceptor groups in the active-site of PSMA resulting in tighter binding. An analogous N-phosphonyl-glutamate exhibited significantly greater inhibitory potency than the parent N-thiophosphonyl-glutamate indicating that the sulfur ligand of the N-thiophosphonyl-glutamates is responsible for less favorable active-site interactions than oxygen, potentially due to steric crowding from the longer P-S bond or as a result of active-site metal substitution of Co(II) for Zn(II) arising from assay conditions. 相似文献
10.
Wu LY Anderson MO Toriyabe Y Maung J Campbell TY Tajon C Kazak M Moser J Berkman CE 《Bioorganic & medicinal chemistry》2007,15(23):7434-7443
To identify the pharmacophore of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen (PSMA), a small analog library was designed and screened for inhibitory potency against PSMA. The design of the lead inhibitor was based upon N-acyl derivatives of endogenous substrate folyl-gamma-Glu and incorporates a phosphoramidate group to interact with the PSMA catalytic zinc atoms. The scope of the analog library was designed to test the importance of various functional groups to the inhibitory potency of the lead phosphoramidate. The IC(50) for the lead phosphoramidate inhibitor was 35 nM while the IC(50) values for the analog library presented a range from 0.86 nM to 4.1 microM. Computational docking, utilizing a recently solved X-ray crystal structure of the recombinant protein, along with enzyme inhibition data, was used to propose a pharmacophore model for the PSMA active site. 相似文献