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21.
Flanking markers bracket the neurofibromatosis type 2 (NF2) gene on chromosome 22. 总被引:8,自引:4,他引:4 下载免费PDF全文
G A Rouleau B R Seizinger W Wertelecki J L Haines D W Superneau R L Martuza J F Gusella 《American journal of human genetics》1990,46(2):323-328
Neurofibromatosis 2 or bilateral acoustic neurofibromatosis (NF2) is a severe autosomal dominant disorder characterized by the development of multiple tumors of the nervous system, including meningiomas, gliomas, neurofibromas, ependymomas, and particularly acoustic neuromas. Polymorphic DNA markers have revealed frequent loss of one copy of chromosome 22 in the tumor types associated with NF2. Family studies have demonstrated that the primary defect in NF2 is linked to DNA markers on chromosome 22, suggesting that it involves inactivation of a tumor suppressor gene. We have employed a combination of multipoint linkage analysis and examination of deletions in primary tumor specimens to precisely map the NF2 locus between flanking polymorphic DNA markers on chromosome 22. The 13-cM region bracketed by these markers corresponds to 13% of the genetic length of the long arm of chromosome 22 and is expected to contain less than 5 x 10(6) bp of DNA. The delineation of flanking markers for NF2 should permit accurate presymptomatic and prenatal diagnosis for the disorder and greatly facilitate efforts to isolate the defective gene on the basis of its location. 相似文献
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Ohne Zusammenfassung 相似文献
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Helen E. Driessen Magda S. Fontes Leonie van Stuijvenberg Maike A. Brans Marie‐Jose Goumans Marc A. Vos Toon A. van Veen 《Journal of cellular and molecular medicine》2020,24(15):8417-8429
In the diseased and remodelled heart, increased activity and expression of Ca2+/calmodulin‐dependent protein kinase II (CaMKII), an excess of fibrosis, and a decreased electrical coupling and cellular excitability leads to disturbed calcium homeostasis and tissue integrity. This subsequently leads to increased arrhythmia vulnerability and contractile dysfunction. Here, we investigated the combination of CaMKII inhibition (using genetically modified mice expressing the autocamtide‐3‐related‐peptide (AC3I)) together with eplerenone treatment (AC3I‐Epler) to prevent electrophysiological remodelling, fibrosis and subsequent functional deterioration in a mouse model of chronic pressure overload. We compared AC3I‐Epler mice with mice only subjected to mineralocorticoid receptor (MR) antagonism (WT‐Epler) and mice with only CaMKII inhibition (AC3I‐No). Our data show that a combined CaMKII inhibition together with MR antagonism mitigates contractile deterioration as was manifested by a preservation of ejection fraction, fractional shortening, global longitudinal strain, peak strain and contractile synchronicity. Furthermore, patchy fibrosis formation was reduced, potentially via inhibition of pro‐fibrotic TGF‐β/SMAD3 signalling, which related to a better global contractile performance and a slightly depressed incidence of arrhythmias. Furthermore, the level of patchy fibrosis appeared significantly correlated to eplerenone dose. The addition of eplerenone to CaMKII inhibition potentiates the effects of CaMKII inhibition on pro‐fibrotic pathways. As a result of the applied strategy, limiting patchy fibrosis adheres to a higher synchronicity of contraction and an overall better contractile performance which fits with a tempered arrhythmogenesis. 相似文献
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Nirvana Sadaghianloo Julie Contenti Maeva Dufies Julien Parola Matthieu Rouleau Shinrong Lee Jean-François Peyron Lucilla Fabbri Réda Hassen-Khodja Jacques Pouysségur Frédéric Bost Elixène Jean-Baptiste Alan Dardik Nathalie M. Mazure 《Journal of cellular and molecular medicine》2020,24(5):2931-2941
Arteriovenous fistulas (AVFs) are the preferred vascular access for haemodialysis of patients suffering from end-stage renal disease, a worldwide public health problem. However, they are prone to a high rate of failure due to neointimal hyperplasia and stenosis. This study aimed to determine if osteopontin (OPN) was induced in hypoxia and if OPN could be responsible for driving AVF failure. Identification of new factors that participate in remodelling of AVFs is a challenge. Three cell lines representing the cells of the three layers of the walls of arteries and veins, fibroblasts, smooth muscle cells and endothelial cells, were tested in mono- and co-culture in vitro for OPN expression and secretion in normoxia compared to hypoxia after silencing the hypoxia-inducible factors (HIF-1α, HIF-2α and HIF-1/2α) with siRNA or after treatment with an inhibitor of NF-kB. None of the cells in mono-culture showed OPN induction in hypoxia, whereas cells in co-culture secreted OPN in hypoxia. The changes in oxygenation that occur during AVF maturation up-regulate secretion of OPN through cell-cell interactions between the different cell layers that form AVF, and in turn, these promote endothelial cell proliferation and could participate in neointimal hyperplasia. 相似文献
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The wild currant tomato Solanum pimpinellifolium inhabits a wide range of abiotic habitats across its native range of Ecuador and Peru. Although it has served as a key genetic resource for the improvement of domestic cultivars, little is known about the genetic basis of traits underlying local adaptation in this species, nor what abiotic variables are most important for driving differentiation. Here we use redundancy analysis (RDA) and other multivariate statistical methods (structural equation modelling [SEM] and generalized dissimilarity modelling [GDM]) to quantify the relationship of genomic variation (6,830 single nucleotide polymorphisms [SNPs]) with climate and geography, among 140 wild accessions. RDA, SEM and GDM each identified environment as explaining more genomic variation than geography, suggesting that local adaptation to heterogeneous abiotic habitats may be an important source of genetic diversity in this species. Environmental factors describing temporal variation in precipitation and evaporative demand explained the most SNP variation among accessions, indicating that these forces may represent key selective agents. Lastly, by studying how SNP–environment associations vary throughout the genome (44,064 SNPs), we mapped the location and investigated the functions of loci putatively contributing to climatic adaptations. Together, our findings indicate an important role for selection imposed by the abiotic environment in driving genomic differentiation between populations. 相似文献
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Jian-Jun Jia Roni M Lahr Michael T Solgaard Bruno J Moraes Roberta Pointet An-Dao Yang Giovanna Celucci Tyson E Graber Huy-Dung Hoang Marius
R Niklaus Izabella A Pena Anne K Hollensen Ewan M Smith Malik Chaker-Margot Leonie Anton Christopher Dajadian Mark Livingstone Jaclyn Hearnden Xu-Dong Wang Yonghao Yu Timm Maier Christian K Damgaard Andrea J Berman Tommy Alain Bruno D Fonseca 《Nucleic acids research》2021,49(6):3461
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James J. Lewis Katherine L. Fielding Alison D. Grant Violet N. Chihota Flora Popane Mariette Luttig Dorothy Muller Leonie Coetzee Gavin J. Churchyard 《PloS one》2013,8(11)
Setting
The “Thibela TB” cluster randomised trial of community-wide isoniazid preventive therapy (IPT) to reduce tuberculosis incidence in the South African gold mines.Objectives
To determine the proportion of participants eligible for IPT and the reasons and risk factors for ineligibility, to inform the scale-up of IPT.Design
Cross-sectional survey of participants in intervention clusters (mine shafts) consenting to tuberculosis screening and assessment for eligibility to start IPT.Results
Among 27,126 consenting participants, 94.7% were male, the median age was 41 years, 12.2% reported previous tuberculosis, 0.6% reported ever taking IPT and 2.5% reported currently taking antiretroviral therapy. There were 24,430 (90.1%) assessed as eligible to start IPT, of whom 23,659 started IPT. The most common reasons for ineligibility were having suspected tuberculosis that was subsequently confirmed by a positive smear and/or culture (n=705), excessive alcohol consumption (n=427) and being on tuberculosis treatment at time of initial screen (n=241). Ineligibility was associated with factors including older age, female gender, prior history of tuberculosis and being in “HIV care”. However, at least 78% were eligible for IPT in all of these sub-groups.Conclusions
The vast majority of participants in this community-wide intervention were eligible for IPT. 相似文献29.
Abdullah Al Mamun Munim Mannan Michael J. O'Callaghan Gail M. Williams Jake M. Najman Leonie K. Callaway 《PloS one》2013,8(12)
We have investigated the prospective association between excess gestational weight gain (GWG) and development of diabetes by 21 years post-partum using a community-based large prospective cohort study in Brisbane, Australia. There were 3386 mothers for whom complete data were available on GWG, pre-pregnancy BMI and self-reported diabetes 21 years post-partum. We used The Institute of Medicine (IOM) definition to categorize GWG as inadequate, adequate and excessive. We found 839 (25.78%) mothers gained inadequate weight, 1,353 (39.96%) had adequate weight gain and 1,194 (35.26%) had gained excessive weight during pregnancy. At 21 years post-partum, 8.40% of mothers self-reported a diagnosis of diabetes made by their doctor. In the age adjusted model, we found mothers who gained excess weight during pregnancy were 1.47(1.11,1.94) times more likely to experience diabetes at 21 years post-partum compared to the mothers who gained adequate weight. This association was not explained by the potential confounders including maternal age, parity, education, race, smoking, TV watching and exercise. However, this association was mediated by the current BMI. There was no association for the women who had normal BMI before pregnancy and gained excess weight during pregnancy. The findings of this study suggest that women who gain excess weight during pregnancy are at greater risk of being diagnosed with diabetes in later life. This relationship is likely mediated through the pathway of post-partum weight-retention and obesity. This study adds evidence to the argument that excessive GWG during pregnancy for overweight mothers has long term maternal health implications. 相似文献
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