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排序方式: 共有557条查询结果,搜索用时 15 毫秒
1.
Keith J Murphy Andrew G Foley Alan W O'connell Ciaran M Regan 《Neuropsychopharmacology》2006,31(1):90-100
Recent data suggest that Alzheimer's patients who discontinue treatment with cholinesterase inhibitors have a significantly delayed cognitive decline as compared to patients receiving placebo. Such observations suggest cholinesterase inhibitors to provide a disease-modifying effect as well as symptomatic relief and, moreover, that this benefit remains after drug withdrawal. Consistent with this suggestion, we now demonstrate that chronic administration of tacrine, nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memory-associated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability. As a combination of both interventions failed to further increase basal polysialylated cell frequency, complex environment rearing and chronic drug regimens most likely enhanced cognitive performance by the same mechanism(s). These findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease modifying action of drugs such as cholinesterase inhibitors. Moreover, the molecular and cellular events underpinning neuroplastic responses are identified as novel targets in the search for interventive drug strategies for the treatment of neurodegenerative and neuropsychiatric disorders. 相似文献
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Aisling E. Courtney Ciaran C. Doherty Brian Herron Mark O. McCarron John K. Connolly J. Ashley Jefferson 《American journal of transplantation》2004,4(7):1204-1207
Myositis is a rare complication following renal transplantation and is most commonly the result of drug-mediated myotoxicity. Other causative disorders include viral infection, electrolyte imbalance and myositis of autoimmune origin. We describe a 60-year-old patient who developed acute polymyositis 4 weeks after a 000 human leukocyte antigen (HLA) mismatch cadaveric renal transplant. Following an uncomplicated transplant course with maintenance triple immunosuppression (prednisolone, mycophenolate mofetil and cyclosporine), the patient presented with severe symmetrical proximal muscle weakness associated with a rise in serum creatine kinase to 46800 U/L. Electromyography confirmed myopathic changes and muscle biopsy demonstrated extensive muscle-fiber necrosis with an inflammatory infiltrate. There were no obviously culpable drugs and viral studies were negative. Prompt initiation of high-dose steroid therapy led to clinical and biochemical recovery. Acute polymyositis may occur following renal transplantation. Potential mechanisms include viral antigen transmission or a localized form of graft vs. host disease. 相似文献
4.
Constantine S Mitsiades Vassiliki Poulaki Ciaran McMullan Joseph Negri Galinos Fanourakis Athina Goudopoulou Victoria M Richon Paul A Marks Nicholas Mitsiades 《Clinical cancer research》2005,11(10):3958-3965
Histone deacetylases (HDAC) and histone acetyltransferases exert opposing enzymatic activities that modulate the degree of acetylation of histones and other intracellular molecular targets, thereby regulating gene expression, cellular differentiation, and survival. HDAC inhibition results in accumulation of acetylated histones and induces differentiation and/or apoptosis in transformed cells. In this study, we characterized the effect of two HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and m-carboxycinnamic acid bis-hydroxamide, on thyroid carcinoma cell lines, including lines originating from anaplastic and medullary carcinomas. In these models, both SAHA and m-carboxycinnamic acid bis-hydroxamide induced growth arrest and caspase-mediated apoptosis and increased p21 protein levels, retinoblastoma hypophosphorylation, BH3-interacting domain death agonist cleavage, Bax up-regulation, down-regulation of Bcl-2, A1, and Bcl-x(L) expression, and cleavage of poly(ADP-ribose) polymerase and caspase-8, -9, -3, -7, and -2. Transfection of Bcl-2 cDNA partially suppressed SAHA-induced cell death. SAHA down-regulated the expression of the apoptosis inhibitors FLIP and cIAP-2 and sensitized tumor cells to cytotoxic chemotherapy and death receptor activation. Our studies provide insight into the tumor type-specific mechanisms of antitumor effects of HDAC inhibitors and a framework for future clinical applications of HDAC inhibitors in patients with thyroid cancer, including histologic subtypes (e.g., anaplastic and medullary thyroid carcinomas) for which limited, if any, therapeutic options are available. 相似文献
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Andrea Piccin Ciaran Murphy Elva Eakins Maria Beatrice Rondinelli Massimo Daves Cinzia Vecchiato Dominik Wolf Corrina Mc Mahon Owen P. Smith 《European journal of haematology》2019,102(4):319-330
Sickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β‐globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso‐occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell‐derived microparticle (MP) generation is also involved in the vaso‐occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US‐FDA‐approved therapy to prevent painful vaso‐occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L‐glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA. 相似文献
8.
Shelmerdine Susan C. Main Cheryl Hutchinson John Ciaran Langan Dean Sebire Neil J. Arthurs Owen J. 《International journal of legal medicine》2018,132(6):1735-1741
International Journal of Legal Medicine - Diffusion-weighted MRI provides information regarding body water movement following death, which may be an imaging marker of post-mortem interval (time... 相似文献
9.
Ciaran O McDonnell James B Semmens Yvonne B Allen Shirley J Jansen D Mark Brooks Michael M D Lawrence-Brown 《Journal of endovascular therapy》2007,14(5):625-629
PURPOSE: To examine if the presence of large iliac arteries is a potential risk factor for the development of a type Ib endoleak (iliac sealing zone) or need for iliac artery-related secondary intervention in patients undergoing endovascular abdominal aortic aneurysm repair. METHODS: The medical notes and all preoperative and postoperative plain abdominal radiographs and computer tomographic scans were reviewed for a consecutive series of 100 patients (89 men; mean age 75 years, range 56-91) with large iliac arteries (mean 19.7 mm, range 16-22) who had Zenith endovascular stent-grafts inserted for management of aortoiliac aneurysmal disease from January 1999 until September 2002. Endpoints were all-cause mortality, aneurysm-related death, endoleak, secondary intervention, secondary interventions, and stent-graft migration. RESULTS: Mean follow-up was 30.1+/-8.3 months; at the last follow-up, 30% of patients were dead, 3% were aneurysm-related. Seven (7%) patients developed a type Ib endoleak, with the remainder being type II (29%), type Ia (2%), type III (1%), and type V (endotension, 1%). Eight (27.5%) type II endoleaks persisted, with the remainder closing spontaneously with sac shrinkage. The iliac artery-related secondary intervention rate was 10%, and the overall secondary intervention rate was 16%. CONCLUSION: Iliac arteries between 16 and 22 mm in diameter may be treated with a cuff to the iliac limb with an expectation of 90% efficacy. Surveillance is required, with a high index of suspicion for type 1b endoleaks. Early secondary iliac intervention with extension to the external iliac artery is recommended if there is an increase in sac size after 6 months. 相似文献