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51.
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Avivit Cahn MD Itamar Raz MD Marc Bonaca MD Ofri Mosenzon MD Sabina A. Murphy MPH Ilan Yanuv MSc Aliza Rozenberg MA John P. H. Wilding MD Deepak L. Bhatt MD Darren K. McGuire MD Ingrid A. M. Gause-Nilsson MD Martin Fredriksson MD Peter A. Johansson MSc Gyorgy Jermendy MD Samy Hadjadj MD Anna Maria Langkilde MD Marc S. Sabatine MD Stephen D. Wiviott MD Lawrence A. Leiter MD 《Diabetes, obesity & metabolism》2020,22(8):1357-1368
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Hypercortisolism due to an ACTH-secreting pituitary adenoma (Cushing’s disease) is a chronic condition associated with high morbidity and mortality if inadequately managed. Pasireotide is a multireceptor-targeted somatostatin analogue and is the only approved medical therapy for Cushing’s disease that treats the underlying cause of the disorder. This paper reviews the available literature for medical-therapy-induced adenoma volume reduction in patients with Cushing’s disease and reports the experience of a 53-year-old surgically, radiologically and medically naïve (de novo) female with a pituitary macroadenoma who declined surgery. This patient was treated with pasireotide as first-line therapy as part of the largest randomized Phase III study evaluating a medical therapy in patients with Cushing’s disease (SOM230B2305 trial). Subcutaneous pasireotide significantly decreased tumor volume, suppressed cortisol secretion, and improved clinical signs and symptoms of Cushing’s disease in this patient. Based on this experience, first-line pasireotide has the potential to achieve substantial tumor volume reduction in addition to significant improvements in cortisol levels and signs and symptoms in patients with Cushing’s disease for whom surgery is not an option. 相似文献
55.
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Targeting stathmin in prostate cancer 总被引:4,自引:0,他引:4
Stathmin is the founding member of a family of microtubule-destabilizing proteins that regulate the dynamics of microtubule polymerization and depolymerization. Stathmin is expressed at high levels in a variety of human cancers and provides an attractive molecule to target in cancer therapies that disrupt the mitotic apparatus. We developed replication-deficient bicistronic adenoviral vectors that coexpress green fluorescent protein and ribozymes that target stathmin mRNA. The therapeutic potential of these recombinant adenoviruses was tested in an experimental androgen-independent LNCaP prostate cancer model. Adenovirus-mediated transfer of anti-stathmin ribozymes resulted in efficient transduction and marked inhibition of stathmin expression in these cells. Cells that were transduced with the anti-stathmin adenoviruses showed a dramatic dose-dependent growth inhibition. This was associated with accumulation of LNCaP cells in the G2-M phases of the cell cycle. A similar dose-dependent inhibition of clonogenic potential was also observed in cells infected with anti-stathmin adenoviruses. Morphologic and biochemical analysis of infected cells showed a marked increase in apoptosis characterized by detachment of the cells, increased chromatin condensation, activation of caspase-3, and fragmentation of internucleosomal DNA. If these findings are confirmed in vivo, it may provide an effective approach for the treatment of prostate cancer. 相似文献
57.
Meredith L. Johnston MBBS Shao Hui Huang MSc John N. Waldron MD Eshetu G. Atenafu MSc Kelvin Chan MD MSc Bernard J. Cummings MBChB Ralph W. Gilbert MD David Goldstein MD Patrick J. Gullane MB Jonathan C. Irish MD MSc Bayardo Perez–Ordonez MD Ilan Weinreb MD Andrew Bayley MD John Cho MD PhD Laura A. Dawson MD Andrew Hope MD Jolie Ringash MD MSc Ian J. Witterick MD Brian O'Sullivan MD John Kim MD 《Head & neck》2016,38(Z1):E820-E826
58.
Impact of p16 expression,nodal status,and smoking on oncologic outcomes of patients with head and neck unknown primary squamous cell carcinoma 下载免费PDF全文
59.
Buck BJ Kerman IA Burghardt PR Koch LG Britton SL Akil H Watson SJ 《Neuroscience letters》2007,421(2):178-183
Although alterations in the function of the neurotransmitter system have been implicated in the pathology of Alzheimer's disease (AD), the mechanisms that underlie this pathological change are not well understood. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key protease in the generation of beta-amyloid, an important trigger protein in the pathogenesis of AD. The expression and activity of BACE1 are increased in the brains of sporadic AD patients, and a role for BACE1 in neurotransmission has been suggested recently. This study examines whether BACE1 plays a role in regulated exocytosis in PC12 cells. Treatment of PC12 cells with a beta-secretase inhibitor reduced stimulus-dependent secretion of neurotransmitters, suggesting a potential role of BACE1 in regulated exocytosis. Using transfected human growth hormone as a reporter for a regulated secretory pathway in PC12 cells, we found that the transient overexpression of BACE1 increased basal secretion in the absence of a stimulus and reduced stimulus-dependent secretion in intact PC12 cells. In digitonin-permeabilized PC12 cells, an overexpression of BACE1 enhanced the Ca2+-independent and ATP-independent component of the secretory pathway. Furthermore, expression of the glycosylation-deficient mutant of BACE1, BACE1N354Q, led to an elevation of basal secretions over that by BACE1 wild-type, suggesting a role of BACE1 glycosylation in basal secretion. These results demonstrate an unknown role for BACE1 in secretion, and suggest that elevated levels of BACE1 in AD brains may contribute to the altered neurotransmitter pathology of AD through stimulation of spontaneous basal secretion under resting conditions. 相似文献
60.
Severe combined immunodeficiency (SCID) is a lethal disease unless allogeneic bone marrow transplantation (BMT), preferably
from a family related HLA identical donor (RID) is given. Previously, some patients received HLA-mismatched related donors
(MMRD) BMT, which often resulted in slow immune reconstitution and variable survival. Alternatively, HLA-matched unrelated
donors (MUD) BMT have been suggested. Recently, we have directly compared outcome of patients with SCID who received either
MMRD or MUD BMT. Survival after MUD BMT was significantly better than after MMRD BMT. Patients who received MUD BMT also had
better engraftment of donor cells and immune reconstitution. Recent reports from other centers confirm these results finding
that MUD BMT provides excellent survival and better immune reconstitution for patients with SCID. In conclusion, MUD BMT appears
vastly superior to MMRD BMT and should be offered as first choice of treatment for patients with SCID when RID is unavailable.
Presented at the First Robert A Good Society Symposium, St. Petersburg, FL 2006. 相似文献