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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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This is an analysis of 37 previously untreated patients with squamous cell carcinoma of the maxillary sinus treated with curative intent at the University of Florida from January 1966 through January 1984. All patients were followed for at least two years and 86 per cent (32/27) were followed for a minimum of five years. Patients were treated for cure with radiation therapy alone (25), surgery alone (1), or surgery and preoperative (6) or postoperative (5) radiation therapy. This study presents the results of treatment and the incidence of treatment-related complications in this group of patients. 相似文献
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Larry E. Davis Mario Kornfeld Herbert S. Mooney Kurt J. Fiedler Kathleen Y. Haaland William W. Orrison Elsa Cernichiari Thomas W. Clarkson 《Annals of neurology》1994,35(6):680-688
For 3 months in 1969 a family in the United States that included a pregnant mother consumed pork containing methylmercury. Children, aged 20, 13, and 8 years and a neonate, developed severe neurological signs. Twenty-two years later, the 2 oldest had cortical blindness or constricted visual fields, diminished hand proprioception, choreoathetosis, and atentional deficits. Magnetic resonance images showed tissue loss in the calcarine and parietal cortices and cerebellar folia. The youngest had quadriplegia, blindness, and severe mental retradation until their deaths. The brain of the 8-year-old who died at age 30 showed cortical atrophy, neuronal loss, and gliosis, most pronounced in the paracentral and parietooccipital regions. The total mercury level in formalin-fixed, left occipital cortex was 1,974 ng/gm as measured by atomic absorption. Regional brain mercury levels correlated with extent of brain damage. A control patient had 38.5 ng of mercury/gm in the occipital cortex. Systemic organs in the patient and a control subject had comparable mercury levels. In mercury-intoxicated rats, we found that only 5 to 10% of total brain mercury was lost by formalin fixation. Brain inorganic mercury in the patient ranged from 82 to 100%. Since inorganic mercury crosses the blood-brain barrier poorly, biotransformation of methyl to inorganic mercury may have occurred after methylmercury crossed the blood-brain barrier, accounting for its persistence in brain and causing part of the brain damage. 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
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Pupils are frequently dilated on the day before cataract surgery and for retinal detachment surgery so the fundus can be examined. This may, however, interfere with pupil mydriasis on the day of surgery. This study looked at the effect of pupil dilation with tropicamide 1% and with cyclopentolate 1% on pupil mydriasis 24 hours later, using phenylephrine 10% and cyclopentolate 1%, in 40 cataract patients. The pupils dilated with cyclopentolate one day previously demonstrated a mean reduction in subsequent mydriasis of 0.73 mm compared with pupils that had been dilated with tropicamide (P less than .0001). The magnitude of this difference was not related to the patient age (P = .12) or to iris color (P = .21). If it is necessary to dilate pupils on the day before surgery, tropicamide 1% rather than cyclopentolate 1% should be used, as it is less likely to interfere with the pupil mydriasis produced with cyclopentolate 1% and phenylephrine 10% on the day of surgery. 相似文献