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Barry W McColl Ailsa L McGregor Andrew Wong Julian D Harris Andrea Amalfitano Sandra Magnoni Andrew H Baker George Dickson Karen Horsburgh 《Journal of cerebral blood flow and metabolism》2007,27(3):477-487
Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy. 相似文献
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Summary In the rat, prolonged administration of the luteinizing, hormone-releasing hormone agonist buserelin (25 μg/kg body wt/day
s.c.) lowers blood estradiol, raises bone resorption, and induces osteopenia. The present study was undertaken to determine
whether withdrawal of buserelin normalizes blood estradiol, slows bone resorption, and corrects buserelin-mediated osteopenia.
Four groups of female rats with45Ca-labeled bones were studied: group 1A received 0.2 ml saline s.c. daily for 4 weeks; group 2A received 0.2 ml buserelin
s.c. daily for 4 weeks; group 1B received 0.2 ml saline s.c. daily for 8 weeks; group 2B received 0.2 ml buserelin s.c. daily
for 4 weeks followed by 0.2 ml saline s.c. daily for 4 weeks. Bone resorption was monitored by measuring urinary45Ca and hydroxyproline. The rats in groups 1A and 2A were killed after 4 weeks and those in groups 1B and 2B after 8 weeks.
The mineral contents of the femoral bones and the whole skeletons were measured. Buserelin lowered blood estradiol, elevated
urinary45Ca and urinary hydroxyproline, and lowered femur and total body calcium and45Ca in group 2A vs. 1A (P<0.05). By contrast all these measurements became similar in groups 2B and 1B. Thus, osteopenia generated by a 4-week period
of buserelin-mediated hypo-estrogenism is reversible by withdrawing buserelin for 4 weeks. Consequently, buserelin administration
and withdrawal may be used to study effects of inducing and reversing estrogen-deficiency bone loss in the rat. 相似文献
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Ruth Naughton-Doe MSc PhD Ailsa Cameron MSc John Carpenter B.Sc. Cert. App. Soc. Studies C.Q.S.W. C.Psychol. AFBPsS DSc 《Health & social care in the community》2021,29(5):1285-1295
This paper explores the potential contribution of timebanking, an innovative volunteering scheme, to the co-production of preventive social care with adults in England. Interest in volunteering in social care has increased as one proposed solution to the international crisis of a rising demand for services in juxtaposition with decreased resources. Volunteering has been particularly promoted in preventive services that prevent or delay care needs arising. Despite sustained interest in volunteering and co-production in social care, little is known about how theory translates into practice. Reporting implementation data from a Realistic Evaluation of six case studies in England, this paper explores one volunteering scheme, timebanking. The research explores how timebanks were working, what contribution they can make to adult social care, and whether they are an example of co-production. Data collected included interviews, focus groups or open question responses on surveys from 84 timebank members, and semi-structured interviews with 13 timebank staff. Each timebank was visited at least twice, and all timebank activity was analysed for a period of 12 months. Data were triangulated to improve reliability. The research found that in practice, timebanks were not working as described in theory, there were small numbers of person-to-person exchanges and some timebanks had abandoned this exchange model. Timebanks faced significant implementation challenges including managing risk and safeguarding and the associated bureaucracy, a paternalistic professional culture and the complexity of the timebank mechanism which required adequate resources. Lessons for timebanks are identified, as well as transferable lessons about co-production and volunteering in social care if such schemes are to be successful in the future. 相似文献
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Pablo Canales-Herrerias Etienne Crickx Matteo Broketa Aurlien Sokal Guilhem Chenon Imane Azzaoui Alexis Vandenberghe Angga Perima Bruno Iannascoli Odile Richard-Le Goff Carlos Castrillon Guillaume Mottet Delphine Sterlin Ailsa Robbins Marc Michel Patrick England Gael A. Millot Klaus Eyer Jean Baudry Matthieu Mahevas Pierre Bruhns 《The Journal of clinical investigation》2022,132(12)
The major therapeutic goal for immune thrombocytopenic purpura (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. Eighty percent of patients with ITP possess anti–integrin αIIbβ3 IgG autoantibodies that cause platelet opsonization and phagocytosis. The spleen is considered the primary site of autoantibody production by autoreactive B cells and platelet destruction. The immediate failure in approximately 50% of patients to recover a normal platelet count after anti-CD20 rituximab-mediated B cell depletion and splenectomy suggests that autoreactive, rituximab-resistant, IgG-secreting B cells (IgG-SCs) reside in other anatomical compartments. We analyzed more than 3,300 single IgG-SCs from spleen, bone marrow, and/or blood of 27 patients with ITP, revealing high interindividual variability in affinity for αIIbβ3, with variations over 3 logs. IgG-SC dissemination and range of affinities were, however, similar for each patient. Longitudinal analysis of autoreactive IgG-SCs upon treatment with the anti-CD38 mAb daratumumab demonstrated variable outcomes, from complete remission to failure with persistence of high-affinity anti–αIIbβ3 IgG-SCs in the bone marrow. This study demonstrates the existence and dissemination of high-affinity autoreactive plasma cells in multiple anatomical compartments of patients with ITP that may cause the failure of current therapies. 相似文献
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