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1.
Veroniqa Lundbäck Agne Kulyte Rona J. Strawbridge Mikael Ryden Peter Arner Claude Marcus Ingrid Dahlman 《Diabetologia》2018,61(5):1112-1123
Aims/hypothesis
By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs).Methods
Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women. Basal lipolytic activity was measured as glycerol release from adipose tissue explants. Adipocytes were isolated and insulin-stimulated incorporation of radiolabelled glucose into lipids was used to quantify adipocyte insulin sensitivity. Small interfering RNA-mediated knockout in human mesenchymal stem cells was used for functional evaluation of genes.Results
Adipose expression of 48 of the studied candidate genes associated significantly with FSI, whereas expression of 24, 17 and 2 genes, respectively, associated with adipocyte insulin sensitivity, lipolysis and/or WAT morphology (i.e. fat cell size relative to total body fat mass). Four genetic loci contained eQTLs. In one chromosome 4 locus (rs3822072), the FSI-increasing allele associated with lower FAM13A expression and FAM13A expression associated with a beneficial metabolic profile including decreased WAT lipolysis (regression coefficient, R?=??0.50, p?=?5.6?×?10?7). Knockdown of FAM13A increased lipolysis by ~1.5-fold and the expression of LIPE (encoding hormone-sensitive lipase, a rate-limiting enzyme in lipolysis). At the chromosome 7 locus (rs1167800), the FSI-increasing allele associated with lower POM121C expression. Consistent with an insulin-sensitising function, POM121C expression associated with systemic insulin sensitivity (R?=??0.22, p?=?2.0?×?10?2), adipocyte insulin sensitivity (R?=?0.28, p?=?3.4?×?10?3) and adipose hyperplasia (R?=??0.29, p?=?2.6?×?10?2). POM121C knockdown decreased expression of all adipocyte-specific markers by 25–50%, suggesting that POM121C is necessary for adipogenesis.Conclusions/interpretation
Gene expression and adipocyte functional studies support the notion that FAM13A and POM121C control adipocyte lipolysis and adipogenesis, respectively, and might thereby be involved in genetic control of systemic insulin sensitivity.2.
Sergio Daga Jie Ding Constantinos Deltas Judy Savige Beata S. Lipska-Zitkiewicz Julia Hoefele Frances Flinter Daniel P. Gale Marina Aksenova Hirofumi Kai Laura Perin Moumita Barua Roser Torra Jeff H. Miner Laura Massella Danica Galei Ljubanovi Rachel Lennon Andr B. Weinstock Bertrand Knebelmann Agne Cerkauskaite Susie Gear Oliver Gross A. Neil Turner Margherita Baldassarri Anna Maria Pinto Alessandra Renieri 《European journal of human genetics : EJHG》2022,30(5):507
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Hannes Schmidt Agne Stonkute René Jüttner Doris Koesling Andreas Friebe Fritz G. Rathjen 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(39):16847-16852
Neuronal circuits are shaped during development by the coordinated action of guidance factors and signals that regulate axonal branching. Unlike guidance cues, the molecules and signaling cascades that underlie axonal branching remain to be resolved. Here we show that the secreted molecule C-type natriuretic peptide (CNP) induces a cGMP signaling cascade via its receptor particulate guanylyl cyclase Npr2 which is essential for sensory axon bifurcation at the dorsal root entry zone (DREZ) of the spinal cord. In contrast, another form of sensory axon branching—collateral formation—is not affected by this pathway. We also demonstrate that cGMP signaling via the nitric oxide-stimulated soluble guanylyl cyclase system (NO-GC) is dispensable for sensory axon branching. Functionally, the bifurcation error in CNP mutant mice is maintained at mature stages and results in a reduced input on secondary neurons as detected by patch-clamp recordings. 相似文献
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Tyrer P Balod A Germanavicius A McDonald A Varadan M Thomas J 《The International journal of social psychiatry》2007,53(6):498-506
BACKGROUND: There is current uncertainty over the future of assertive community and outreach teams in view of recent evidence suggesting that they no longer reduce hospital admissions. Despite this, assertive teams remain popular among practitioners. AIMS: To examine the views of assertive community team members and other mental health professionals in London (UK) and Vilnius (Lithuania) to determine important differences in attitudes. METHOD: A questionnaire, involving the assessment of statements giving common opinions on assertive community teams, was given to 62 staff in Vilnius, Lithuania and West London, UK, 33 from assertive community or outreach teams and 29 from other mental health professionals. RESULTS: The results of the questionnaire showed that personnel in experienced assertive outreach teams in London believed that they gave more intensive care (p < 0.001), felt it of greater value to see patients in the community (p < 0.001) and were not just well-resourced community teams with low caseloads (p < 0.01) than did other groups, but they placed lower value on assertiveness (p = 0.04) and comprehensive care (p < 0.04). These differences were less marked in Lithuania where staff regarded home treatment as similar to clinic treatment and were more supportive of comprehensive care. CONCLUSION: The results suggest that in experienced community teams the notion of assertiveness has become less important in planned intensive community care and so the term ACT may be outmoded. However, for countries such as Lithuania, somewhat similar to the United States in 1972 when ACT began, the original principles are still appropriate and 'assertive' is a major component of their effectiveness. 相似文献
8.
Agne Laucyte-Cibulskiene Evelina Boreikaite Gediminas Aucina Migle Gudynaite Ilona Rudminiene Sigita Anisko 《Renal failure》2018,40(1):201-208
Vascular calcification (VC) is linked to post-transplant cardiovascular events and hypercalcemia which may influence kidney graft function in the long term. We aimed to evaluate whether pretransplant aortic arch calcification (AoAC) can predict post-transplant cardiovascular or cerebrovascular events (CVEs), and to assess its association with post-transplant plasma calcium levels and renal function in one-year follow-up. Our single-center observational prospective study enrolled 37 kidney transplant recipients (KTR) without previous history of vascular events. Two radiologists evaluated pretransplant AoAC on chest X-ray as suggested by Ogawa et al. in 2009. Cohen’s kappa coefficient was 0.71. The mismatching results were repeatedly reviewed and resulted in consensus. Carotid-femoral (cfPWV) and carotid-radial pulse wave velocity (crPWV) was measured using applanation tonometry before and one year after transplantation. Patient clinical, biochemical data, and cardiovascular/CVE rate were monitored within 1 year. We found out that eGFR1year correlated with eGFRdischarge and calcium based on hospital discharge data (β?=?0.563, p?=?.004 and β?=?51.360, p?=?.026, respectively). Multivariate linear regression revealed that donor age, donor gender, and recipient eGFRdischarge (R-squared 0.65, p?=?.002) better predict eGFR1year than AoAC combined with recipient eGFRdischarge (R-squared 0.35, p?=?.006). During 1-year follow-up, four (10.81%) patients experienced cardiovascular events, which were predicted by PWV ratio (HR 7.549, p?=?.045), but not related to AoAC score (HR 1.044, p?=?.158). In conclusion, KTR without previous vascular events have quite low cardiovascular/CVE rate within 1-year follow-up. VC evaluated as AoAC on pretransplant chest X-ray together with recipient eGFRdischarge could be related to kidney function in one-year follow-up. 相似文献
9.
Alberto M. Leopaldi Krzysztof Wrobel Giovanni Speziali Sjoerd van Tuijl Agne Drasutiene W. Randolph Chitwood 《The Journal of thoracic and cardiovascular surgery》2018,155(1):147-155
Objective
Previously, cardiac surgeons and cardiologists learned to operate new clinical devices for the first time in the operating room or catheterization laboratory. We describe a biosimulator that recapitulates normal heart valve physiology with associated real-time hemodynamic performance.Methods
To highlight the advantages of this simulation platform, transventricular extruded polytetrafluoroethylene artificial chordae were attached to repair flail or prolapsing mitral valve leaflets. Guidance for key repair steps was by 2-dimensional/3-dimensional echocardiography and simultaneous intracardiac videoscopy.Results
Multiple surgeons have assessed the use of this biosimulator during artificial chordae implantations. This simulation platform recapitulates normal and pathologic mitral valve function with associated hemodynamic changes. Clinical situations were replicated in the simulator and echocardiography was used for navigation, followed by videoscopic confirmation.Conclusions
This beating heart biosimulator reproduces prolapsing mitral leaflet pathology. It may be the ideal platform for surgeon and cardiologist training on many transcatheter and beating heart procedures. 相似文献10.
Agne Babusyte Jolanta Jeroch Rimantas Stakauskas Raimundas Sakalauskas 《Central European Journal of Medicine》2009,4(2):245-252
Neutrophils are a major source of reactive oxygen species (ROS). The role of airway mucous on ROS production is unknown. The
aim of our study was to investigate the direct influence of bronchoalveolar lavage fluid (BALF) and induced sputum (IS) alone
or in combination with chemical/biological stimulus on ROS production in peripheral blood neutrophils during chronic obstructive
pulmonary disease (COPD). Neutrophils were isolated from peripheral blood of 47 patients with moderate COPD and 14 healthy
individuals (HI). BALF/RPMI (1:1) or IS/RPMI (1:1) from COPD patients were used to stimulate neutrophils alone or in combination
with phorbolmyristate- acetate (PMA) (0.1–30 nM) or Staphylococcus aureus bacteria (0.7–500 bact/neutrophil). Relative generation
of ROS was measured flow cytometrically. BALF/RPMI and in combination with relatively low PMA or all bacteria concentrations
stimulated ROS; while, combination with relatively high PMA concentrations suppressed ROS in of COPD patients and HI. IS/RPMI
and its combination with PMA inhibited ROS generation in both groups; whereas, IS stimulated or had a tendency to stimulate
ROS production with relatively high bacteria concentrations. In conclusion, BALF and IS directly or in combination with chemical/biological
factors modulated ROS production. This effect was stronger in neutrophils from COPD patients and depended on chemical/biological
stimulus intensity. 相似文献