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A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews. 总被引:7,自引:2,他引:5 下载免费PDF全文
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
3.
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
4.
Background
Geographic variation in traditional cardiovascular disease (CVD) risk factors has been observed among women in the US. It is not known whether state-level variation in cardiovascular inflammation exists or could be explained by traditional clinical risk factors and behavioral lifestyle factors.Methods and Results
We used multilevel linear regression to estimate state-level variation in inflammatory biomarker patterns adjusted for clinical and lifestyle characteristics among 26,029 women free of CVD. Participants derived from the Women''s Health Study, a national cohort of healthy middle-aged and older women. Inflammatory biomarker patterns (plasma levels of high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen) were compared to state-level patterns of traditional CVD risk factors and global risk scores. We found that all three inflammatory biomarkers exhibited significant state-level variation including hsCRP (lowest vs. highest state median 1.3 mg/L vs. 2.7 mg/L, unadjusted random effect estimate 1st to 99th percentile range for log hsCRP 0.52, p<.001), sICAM-1 (325 ng/ml vs. 366ng/ml, unadjusted random effect estimate 1st to 99th percentile range 0.44, p<.001), and fibrinogen (322 mg/dL vs. 367 mg/dL, unadjusted random effect estimate 1st to 99th percentile range 0.41, p = .001). Neither demographic, clinical or lifestyle characteristics explained away state-level effects in biomarker patterns. Southern and Appalachian states (Arkansas, West Virginia) had the highest inflammatory biomarker values. Regional geographic patterns of traditional CVD risk factors and risk scores did not completely overlap with biomarkers of inflammation.Conclusions
There is state-level geographic variation in inflammatory biomarkers among otherwise healthy women that cannot be completely attributed to traditional clinical risk factors or lifestyle characteristics. Future research should aim to identify additional factors that may explain geographic variation in biomarkers of inflammation among healthy women. 相似文献5.
6.
目的:观察并分析奥关拉唑联合法莫替丁治疗反流性食管炎的临床效果。方法:选取2008年5月至2012年5月在本院确诊并治疗的反流性食管炎患者45例,随机平均分为三组。联合用药组(15例):每日早餐前口服20mg奥关拉唑,睡前口服20mg法莫替丁;奥关拉唑组(15例):每日口服两次奥美拉唑,每次20mg;法莫替丁组(15例):每日口服两次法莫替丁,每次20mg。每组的治疗时间均为8周。在内镜指导下观察并比较三组患者的胸痛、反酸和烧心等主要病征的改善情况,综合评价三种治疗方法的临床疗效。结果:联合用药组较其他两组获得的疗效更明显,患者的症状得到较好的改善,差异有统计学意义(P〈0.05)。结论:奥美拉唑联合法莫替丁能够有效地抑制胃酸的分泌,对于反流性食管炎的,临床治疗具有良好的效果。 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.
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
9.
Temperature is one of the main factors that determine sexual reproduction in terrestrial and emergent aquatic plant species. The effect of temperature on sexual reproduction and seed production of Glyceria maxima (Hartm.) Holmb. in the southern hemisphere is unknown. Glyceria maxima collections in February 2010 at three isolated infestations in KwaZulu-Natal failed to yield a single seed, only empty panicles. Laboratory experiments showed that vernalisation had no consistent effect on seed production. Field- and laboratory-grown plants produced seeds in the 2010/2011 season, because of having sufficient time at optimum temperatures required for seed production (1 491 and 1 585 hours, respectively), compared to a shorter period (1 352 hours) of suitable temperatures during the 2009/2010 growing season. An inadequate period of optimum temperatures (15–25°C) during seed production resulted in the lack of seeds in the field in the 2009/2010 growing season. This study showed that temperature and duration of exposure thereto during the seed-production period play vital roles in G. maxima sexual reproduction. 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