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51.
Vernica Bidinotto Brito Leopoldo Vinicius Martins Nascimento Dinara Jaqueline Moura Jenifer Saffi 《Arquivos brasileiros de cardiologia》2021,117(6):1147
BackgroundDoxorubicin (DOX) is frequently used to treat many types of cancers, despite its dose-dependent cardiotoxicity. Alternatively, resveratrol is a polyphenol that has shown useful cardioprotective effects in many heart dysfunction models.ObjectiveThis study investigated whether resveratrol treatment in pregnant rats protects against doxorubicin-induced toxicity in offspring cardiomyocytes.MethodsWistar rats (n=8) were supplemented with dietary resveratrol during pregnancy. Upon the offspring’s birth, hearts (9-11) were used to obtain the primary culture of cardiomyocytes. DOX-induced cardiotoxicity and the effects of resveratrol supplementation were evaluated by oxidative stress markers, such as dichlorofluorescein diacetate oxidation, decrease in the activity of antioxidant enzymes, and oxidation of total sulfhydryl content, in addition to cell viability evaluation, DNA damage generation, and DNA damage repair response. A value of p<0.05 was considered statistically significant.ResultsNeonatal cardiomyocytes from resveratrol supplemented rats exhibiting an increase (p<0.01) in cell viability and lower (p<0.0001) apoptotic/necrotic cells after DOX treatment, which correlates with the activities of antioxidant enzymes and dichlorofluorescein production. Moreover, resveratrol protected cardiomyocytes from DOX-induced DNA damage, showing a decrease (p<0.05) in DNA breaks induced by oxidative stress, evaluated by the activity of DNA-repair enzymes endonuclease III and formamidopyrimidine glycosylase. Supplementation with resveratrol increased (p<0.05) the expression of the repair protein Sirt6 in the cardiomyocytes of the pups.ConclusionThis research indicates that supplementation with resveratrol during the gestational period has a notable cardioprotective effect on the offspring’s heart against DOX-induced toxicity, which may well be due to its antioxidant function, and the increase in the DNA damage repair response. 相似文献
52.
Dinara Samarkanova Sara Martin Laia Bisbe Javier Puig Marta Calatayud-Pinuaga Luciano Rodriguez Carmen Azqueta Ruth Coll Ricardo Casaroli-Marano Alejandro Madrigal Paolo Rebulla Sergio Querol 《Trasfusione del sangue》2021,19(4):347
BackgroundCurrent treatments for several corneal lesions show limited efficacy. Here we report the clinical evaluation of the efficacy of a novel eye drop preparation produced in a public cord blood (CB) bank.Materials and methodsIn a multicentre, retrospective, consecutive case study we evaluated 33 patients (46 eyes) unresponsive to conventional treatments who required urgent intervention. The patients were given allogeneic eye drops obtained from cord blood platelet lysate (CBED) to treat severe ocular surface lesions under a compassionate use protocol. The CBED were prepared from CB units donated for haematopoietic stem cell transplantation that did not contain the minimum stem cell dose required for this use. Patients were grouped by acute conditions (neurotrophic ulcers: group I; other corneal ulcers: group II; corneal burns: group III), and chronic conditions (ocular graft-versus-host disease: group IV; severe dry eye syndrome: group V). The patients received one or two drops of the product to the affected eye four to six times per day for 19 days. A further 19-day cycle of treatment could be repeated according to the initial clinical response.ResultsPatients received a median of 19 CBED vials (interquartile range 19–57, range 19–442) to complete the therapy. Group I–II–III patients showed full and partial ulcer recovery in 25 (78%) and six (19%) eyes respectively. One eye (3%) did not respond to treatment. For groups IV–V improvement was reported for 12 (85%) eyes and lesions worsened on treatment in both eyes (15%) of one patient. No severe adverse events were directly attributed to CBED.DiscussionPromptly available CBED resulted in a well-tolerated allogeneic treatment that showed evidence of efficacy in this cohort of patients. These positive results support further studies on CBED from platelet lysate as a novel product of CB banks. A prospective clinical trial in neurotrophic keratitis () is ongoing to confirm these preliminary data. NCT03084861相似文献
53.
Psychological stress may affect up to 18% of all pregnant women, altering the function of both neuroendocrine and immune systems. Distress conditions may directly change the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased cortisol levels and associated changes in cellular immunity. Psychological events such as high stress levels, anxiety or depression may directly or indirectly affect pregnancy and may thus lead to pre-eclampsia (PE). Here, we suggest that distress conditions during pregnancy may lead the development of PE by enhancing in vivo cortisol levels. High cortisol levels are associated with hypertension and endothelial dysfunction, features often observed in patients with PE. Lymphocytes from patients with high cortisol levels may have a reduced sensitivity to the synthetic glucocorticoid dexamethasone (DEX). Stress-related steroid resistance may disrupt the HPA axis, leading to post-natal detrimental effects such as increased allostatic load, increased pro-inflammatory cytokine levels and even depression in the offspring. 相似文献
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56.
Activity elicits capture of dense-core vesicles (DCVs) that transit through resting Drosophila synaptic boutons to produce a rebound in presynaptic neuropeptide content following release. The onset of capture overlaps
with an increase in the mobility of DCVs already present in synaptic boutons. Vesicle mobilization requires Ca2+-induced Ca2+ release by presynaptic endoplasmic reticulum (ER) ryanodine receptors (RyRs) that in turn stimulates Ca2+/calmodulin-dependent kinase II (CamKII). Here we show that the same signaling is required for activity-dependent capture
of transiting DCVs. Specifically, the CamKII inhibitor KN-93, but not its inactive analog KN-92, eliminated the rebound replacement
of neuropeptidergic DCVs in synaptic boutons. Furthermore, pharmacologically or genetically inhibiting neuronal sarco-endoplasmic
reticulum calcium ATPase to deplete presynaptic ER Ca2+ stores or directly inhibiting RyRs prevented the capture response. These results show that the presynaptic RyR–CamKII pathway,
which triggers mobilization of resident synaptic DCVs to facilitate exocytosis, also mediates activity-dependent capture of
transiting DCVs to replenish neuropeptide stores. 相似文献
57.
58.
Timur Saliev Dinara Begimbetova Dinara Baiskhanova Danysh Abetov Ulykbek Kairov Charles P. Gilman Bakhyt Matkarimov Katsuro Tachibana 《Journal of Medical Ultrasonics》2018,45(1):31-39
Purpose
To scrutinize the apoptotic and genotoxic effects of low-intensity ultrasound and an ultrasound contrast agent (SonoVue; Bracco Diagnostics Inc., EU) on human peripheral mononuclear blood cells (PMBCs).Methods
PMBCs were subjected to a low-intensity ultrasound field (1-MHz frequency; spatial peak temporal average intensity 0.18 W/cm2) followed by analysis for apoptosis and DNA damage (single-strand breaks + double-strand breaks). The comet assay was then repeated after 2 h to examine the ability of cells to repair DNA breaks.Results
The results demonstrated that low-intensity ultrasound was capable of selectively inducing apoptosis in leukemic PMBCs, but not in healthy cells. The introduction of ultrasound contrast agent SonoVue resulted in an increase in apoptosis in both groups. DNA analysis after ultrasound exposure indicated that ultrasound triggered DNA damage in leukemic PMBCs (66.05 ± 13.36%), while the damage was minimal (7.01 ± 0.89%) in control PMBCs. However, both cell lines demonstrated an ability to repair DNA single- and double-strand breaks 2 h after sonication.Conclusions
The study demonstrated that low-intensity ultrasound selectively induced apoptosis in cancer PMBCs. Ultrasound-induced DNA damage was observed primarily in leukemic PMBCs. Nevertheless, both cell lines were able to repair ultrasound-mediated DNA strand breaks.59.
Fuat Kurbanov Yasuhito Tanaka Dildora Avazova Anis Khan Fuminaka Sugauchi Nataliya Kan Dinara Kurbanova-Khudayberganova Aziza Khikmatullaeva Erkin Musabaev Masashi Mizokami 《Hepatology research》2008,38(5):457-464
Aim: A series of recent studies have indicated the presence of natural intergenotypic recombinant hepatitis C virus (HCV) strains in distinct parts of the world. The majority of the current genotyping methods are based on analysis of either 5'UTR, structural (Core/E1/E2) or non-structural (NS5B) genomic regions of the virus.
Methods: In the present study, based on both structural and non-structural regions, we determined the genotype of 55 anti-HCV-positive intravenous drug users (IDUs) in Uzbekistan.
Results: HCV-3a (67.3%) was the most prevalent genotype in this cohort, followed by HCV-1b (27.3%). A discrepancy in results was observed between structural and non-structural regions in one case (1.8%). Phylogenetically this strain was related to the previously reported RF1_2k/1b variant. Based on accumulated sequences, specific primers were designed for polymerase chain reaction (PCR) spanning the tentative intergenotypic crossover point of RF1_2k/1b. The sensitivity and specificity of the method were assessed using generated template clones of HCV-1b, 2a, 2 k and RF1_2k/1b. The method was applied to 55 cases in the present study and only one case showed a positive result, indicating that in these individuals, the variant is not present as a minor quasispecies clone.
Conclusion: In conclusion, the finding of RF1_2k/1b in Central Asia indicates that the variant has wide geographic distribution. The PCR-based screening method developed in this study should be useful in further epidemiological and clinical studies on the recombination phenomenon in HCV. 相似文献
Methods: In the present study, based on both structural and non-structural regions, we determined the genotype of 55 anti-HCV-positive intravenous drug users (IDUs) in Uzbekistan.
Results: HCV-3a (67.3%) was the most prevalent genotype in this cohort, followed by HCV-1b (27.3%). A discrepancy in results was observed between structural and non-structural regions in one case (1.8%). Phylogenetically this strain was related to the previously reported RF1_2k/1b variant. Based on accumulated sequences, specific primers were designed for polymerase chain reaction (PCR) spanning the tentative intergenotypic crossover point of RF1_2k/1b. The sensitivity and specificity of the method were assessed using generated template clones of HCV-1b, 2a, 2 k and RF1_2k/1b. The method was applied to 55 cases in the present study and only one case showed a positive result, indicating that in these individuals, the variant is not present as a minor quasispecies clone.
Conclusion: In conclusion, the finding of RF1_2k/1b in Central Asia indicates that the variant has wide geographic distribution. The PCR-based screening method developed in this study should be useful in further epidemiological and clinical studies on the recombination phenomenon in HCV. 相似文献
60.
Nurkeldi Turebekov Karlygash Abdiyeva Ravilya Yegemberdiyeva Andrey Kuznetsov Andrey Dmitrovskiy Lyazzat Yeraliyeva Zhanna Shapiyeva Dinara Batyrbayeva Nur Tukhanova Anna Shin Lyazzat Musralina Michael Hoelscher Guenter Froeschl Gerhard Dobler Klaus Freimueller Edith Wagner Stefan Frey Sandra Essbauer 《The American journal of tropical medicine and hygiene》2021,104(6):2000