首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   88篇
  免费   4篇
  2021年   1篇
  2018年   1篇
  2016年   3篇
  2015年   5篇
  2014年   4篇
  2013年   8篇
  2012年   11篇
  2011年   6篇
  2010年   5篇
  2008年   6篇
  2007年   4篇
  2006年   4篇
  2005年   6篇
  2004年   1篇
  2003年   6篇
  2002年   2篇
  2001年   1篇
  2000年   1篇
  1999年   1篇
  1998年   1篇
  1997年   2篇
  1996年   1篇
  1992年   1篇
  1991年   1篇
  1989年   1篇
  1988年   2篇
  1987年   1篇
  1986年   1篇
  1985年   1篇
  1983年   1篇
  1976年   1篇
  1973年   1篇
  1970年   1篇
排序方式: 共有92条查询结果,搜索用时 203 毫秒
1.
A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.  相似文献   
2.

Background

Sex and Gender Medicine is a novel discipline that provides equitable medical care for society and improves outcomes for both male and female patients. The integration of sex- and gender-specific knowledge into medical curricula is limited due to adequate learning material, systematic teacher training and an innovative communication strategy. We aimed at initiating an e-learning and knowledge-sharing platform for Sex and Gender Medicine, the eGender platform (http://egender.charite.de), to ensure that future doctors and health professionals will have adequate knowledge and communication skills on sex and gender differences in order to make informed decisions for their patients.

Methods

The web-based eGender knowledge-sharing platform was designed to support the blended learning pedagogical teaching concept and follows the didactic concept of constructivism. Learning materials developed by Sex and Gender Medicine experts of seven universities have been used as the basis for the new learning tools. The content of these tools is patient-centered and provides add-on information on gender-sensitive aspects of diseases. The structural part of eGender was designed and developed using the open source e-learning platform Moodle. The eGender platform comprises an English and a German version of e-learning modules: one focusing on basic knowledge and seven on specific medical disciplines. Each module consists of several courses corresponding to a disease or symptom complex. Self-organized learning has to be managed by using different learning tools, e.g., texts and audiovisual material, tools for online communication and collaborative work.

Results

More than 90 users from Europe registered for the eGender Medicine learning modules. The most frequently accessed module was “Gender Medicine—Basics” and the users favored discussion forums. These e-learning modules fulfill the quality criteria for higher education and are used within the elective Master Module “Gender Medicine—Basics” implemented into the accredited Master of Public Health at Charité—Berlin.

Conclusions

The eGender platform is a flexible and user-friendly electronical knowledge-sharing platform providing evidence-based high-quality learning material used by a growing number of registered users. The eGender Medicine learning modules could be key in the reform of medical curricula to integrate Sex and Gender Medicine into the education of health professionals.
  相似文献   
3.
The 2'-C-difluoromethylated nucleoside 4 was synthesized starting from uridine. 4 was then converted to the 3'-O-phosphoramidite derivative 5 and was incorporated into a hammerhead ribozyme (7). The cleavage characteristics of the modified oligonucleotide have been analysed.  相似文献   
4.
The diploid genome of the pathogenic yeast Candida albicans exhibits a high degree of heterozygosity. Genomic alterations that result in a loss of heterozygosity at specific loci may affect phenotypes and confer a selective advantage under certain conditions. Such genomic rearrangements can also occur during the construction of C. albicans mutants and remain undetected. The SAP2 gene on chromosome R encodes a secreted aspartic protease that is induced and required for growth of C. albicans when proteins are the only available nitrogen source. In strain SC5314, the two SAP2 alleles are functionally divergent because of differences in their regulation. Basal expression of the SAP2-2 allele, but not the SAP2-1 allele, provides the proteolytic degradation products that serve as inducers for full SAP2 induction. A triple mutant lacking the SAP4, SAP5, and SAP6 genes, which are located on chromosome 6, has previously been reported to have a growth defect on proteins, suggesting that one of the encoded proteases is required for SAP2 expression. Here we show that this sap4Δ sap5Δ sap6Δ mutant has become homozygous for chromosome R and lost the SAP2-2 allele. Replacement of one of the SAP2-1 copies in this strain by SAP2-2 and its regulatory region restored the ability of the sap4Δ sap5Δ sap6Δ mutant to utilize proteins as the sole nitrogen source. This is an illustrative example of how loss of heterozygosity at a different genomic locus can cause the mutant phenotype attributed to targeted deletion of a specific gene in C. albicans.  相似文献   
5.
Deficiency of acid sphingomyelinase (ASM), an enzyme responsible for producing a pro-apoptotic second messenger ceramide, has previously been shown to promote the survival of fetal mouse oocytes in vivo and to protect oocytes from chemotherapy-induced apoptosis in vitro. Here we investigated the effects of ASM deficiency on testicular germ cell development and on the ability of germ cells to undergo apoptosis. At the age of 20 weeks, ASM knock-out (ASMKO) sperm concentrations were comparable with wild-type (WT) sperm concentrations, whereas sperm motility was seriously affected. ASMKO testes contained significantly elevated levels of sphingomyelin at the age of 8 weeks as detected by high-performance, thin-layer chromatography. Electron microscopy revealed that the testes started to accumulate pathological vesicles in Sertoli cells and in the interstitium at the age of 21 days. Irradiation of WT and ASMKO mice did not elevate intratesticular ceramide levels at 16 h after irradiation. In situ end labeling of apoptotic cells also showed a similar degree of cell death in both groups. After a 21-day recovery period, the numbers of primary spermatocytes and spermatogonia at G2 as well as spermatids were essentially the same in the WT and ASMKO testes, as detected by flow cytometry. In serum-free cultures both ASMKO and WT germ cells showed a significant increase in the level of ceramide, as well as massive apoptosis. In conclusion, ASM is required for maintenance of normal sphingomyelin levels in the testis and for normal sperm motility, but not for testicular ceramide production or for the ability of the germ cells to undergo apoptosis.  相似文献   
6.
Dunkel Marcel 《FEBS letters》2010,584(11):2433-2439
Vacuolar tandem-pore channels could not be analysed in Xenopus oocytes so far, due to misguided translocation. Owing to the conservation of their pore regions, we were able to prepare functional pore-chimeras between the plasma membrane localised TPK4 and vacuolar TPKs. Thereby, we found evidence that TPK2, TPK3 and TPK5, just like TPK4, form potassium-selective channels with instantaneous current kinetics. Homology modelling and mutational analyses identified a pore-located aspartate residue (Asp110), which is involved in potassium permeation as well as in inward rectification of TPK4. Furthermore, dominant-negative mutations in the selectivity filter of either pore one or two (Asp86, Asp200) rendered TPK4 non-functional. This observation supports the notion that the functional TPK4 channel complex is formed by two subunits.  相似文献   
7.
The purposes of this study were to determine the intervals when placental corticotrophic-releasing hormone (CRH) was most responsive to maternal cortisol. A sample of 203 women each were evaluated at 15, 19, 25 and 31 weeks gestation and followed to term. Placental CRH and maternal adrenocorticotropin hormone (ACTH), B-endorphin and cortisol were determined from plasma. CRH levels increased faster and were higher in women who delivered preterm compared with women who delivered at term (F3,603 = 5.73, p < .001). Simple effects indicated that CRH levels only at 31 weeks predicted preterm birth (F1,201 = 5.53, p = .02). Levels of cortisol were higher in women who delivered preterm at 15 weeks gestation (F1,201 = 4.45, p = .03) with a similar trend at 19 weeks gestation. Hierarchical regression suggested that the influence on birth outcome of maternal cortisol early in pregnancy was mediated by its influence on placental CRH at 31 weeks. Elevated cortisol at 15 weeks predicted the surge in placental CRH at 31 weeks (R = .49, d.f. = 1,199, Fchange = 61.78, p < .0001). Every unit of change in cortisol (microg/dl) at 15 weeks was associated with a 34 unit change of CRH (pg/ml) at 31 weeks. These findings suggested that early detection of stress signals by the placenta stimulated the subsequent release of CRH and resulted in increased risk for preterm delivery.  相似文献   
8.
Philopatry and sex-biased dispersal have a strong influence on population genetic structure, so the study of species dispersal patterns and evolutionary mechanisms shaping them are of great interest. Particularly nongregarious mammalian species present an underexplored field of study: despite their lower levels of sociality compared to group-living species, interactions among individuals do occur, providing opportunities for cryptic kin selection. Among the least gregarious primates are orang-utans (genus: Pongo), in which preferential associations among females have nevertheless been observed, but for which the presence of kin structures was so far unresolved because of the equivocal results of previous genetic studies. To clarify relatedness and dispersal patterns in orang-utans, we examined the largest longitudinal set of individuals with combined genetic, spatial and behavioural data. We found that males had significantly higher mitochondrial DNA (mtDNA) variation and more unique haplotypes, thus underscoring their different maternal ancestries compared to females. Moreover, pedigree reconstruction based on 24 highly polymorphic microsatellite markers and mtDNA haplotypes demonstrated the presence of three matrilineal clusters of generally highly related females with substantially overlapping ranges. In orang-utans and possibly other nongregarious species, comparing average biparental relatedness (r) of males and females to infer sex-biased dispersal is extremely problematic. This is because the opportunistic sampling regime frequently employed in nongregarious species, combined with overlapping space use of distinct matrilineal clusters, leads to a strong downward bias when mtDNA lineage membership is ignored. Thus, in nongregarious species, correct inferences of dispersal can only be achieved by combining several genetic approaches with detailed spatial information.  相似文献   
9.
Klinefelter syndrome (KS) is the most common genetic form of male hypogonadism, but the phenotype becomes evident only after puberty. During childhood, and even during early puberty, pituitary-gonadal function in 47,XXY subjects is relatively normal, but from midpuberty onwards, FSH and LH levels increase to hypergonadotropic levels, inhibin B decreases to undetectable levels, and testosterone after an initial increase levels off at a low or low-normal level. Hence, most adult KS males display a clear hypergonadotropism with a varying degree of androgen deficiency; subsequently, testosterone substitution therapy is widely used to prevent symptoms and sequels of androgen deficiency. Testicular biopsies of prepubertal KS boys have shown preservation of seminiferous tubules with reduced numbers of germ cells, but Sertoli and Leydig cells have appeared normal. The testes in the adult KS male are, however, characterized by extensive fibrosis and hyalinization of the seminiferous tubules, and hyperplasia of the interstitium, but the tubules may show residual foci of spermatogenesis. Introduction of testicular sperm extraction in combination with intracytoplasmic sperm injection techniques has allowed non-mosaic KS males to father children.  相似文献   
10.
The putative two-pore Ca(2+) channel TPC1 has been suggested to be involved in responses to abiotic and biotic stresses. We show that AtTPC1 co-localizes with the K(+)-selective channel AtTPK1 in the vacuolar membrane. Loss of AtTPC1 abolished Ca(2+)-activated slow vacuolar (SV) currents, which were increased in AtTPC1-over-expressing Arabidopsis compared to the wild-type. A Ca(2+)-insensitive vacuolar cation channel, as yet uncharacterized, could be resolved in tpc1-2 knockout plants. The kinetics of ABA- and CO(2)-induced stomatal closure were similar in wild-type and tpc1-2 knockout plants, excluding a role of SV channels in guard-cell signalling in response to these physiological stimuli. ABA-, K(+)-, and Ca(2+)-dependent root growth phenotypes were not changed in tpc1-2 compared to wild-type plants. Given the permeability of SV channels to mono- and divalent cations, the question arises as to whether TPC1 in vivo represents a pathway for Ca(2+) entry into the cytosol. Ca(2+) responses as measured in aequorin-expressing wild-type, tpc1-2 knockout and TPC1-over-expressing plants disprove a contribution of TPC1 to any of the stimulus-induced Ca(2+) signals tested, including abiotic stresses (cold, hyperosmotic, salt and oxidative), elevation in extracellular Ca(2+) concentration and biotic factors (elf18, flg22). In good agreement, stimulus- and Ca(2+)-dependent gene activation was not affected by alterations in TPC1 expression. Together with our finding that the loss of TPC1 did not change the activity of hyperpolarization-activated Ca(2+)-permeable channels in the plasma membrane, we conclude that TPC1, under physiological conditions, functions as a vacuolar cation channel without a major impact on cytosolic Ca(2+) homeostasis.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号