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Mutations in the gene encoding nuclear lamin A (LA) cause the premature aging disease Hutchinson-Gilford Progeria Syndrome. The most common of these mutations results in the expression of a mutant LA, with a 50-aa deletion within its C terminus. In this study, we demonstrate that this deletion leads to a stable farnesylation and carboxymethylation of the mutant LA (LADelta50/progerin). These modifications cause an abnormal association of LADelta50/progerin with membranes during mitosis, which delays the onset and progression of cytokinesis. Furthermore, we demonstrate that the targeting of nuclear envelope/lamina components into daughter cell nuclei in early G(1) is impaired in cells expressing LADelta50/progerin. The mutant LA also appears to be responsible for defects in the retinoblastoma protein-mediated transition into S-phase, most likely by inhibiting the hyperphosphorylation of retinoblastoma protein by cyclin D1/cdk4. These results provide insights into the mechanisms responsible for premature aging and also shed light on the role of lamins in the normal process of human aging.  相似文献   
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Background Laparoscopic antireflux surgery has become an established method of treatment of gastroesophageal reflux disease. This study compares the long-term outcome of total (Nissen) and partial (Toupet) fundoplication, performed in a single institution, by evaluating symptoms and quality of life. Methods 266 patients who underwent laparoscopic Nissen or Toupet fundoplication completed a preoperative reflux symptom questionnaire. Postsurgery symptom evaluation, patient satisfaction and quality of life in reflux and dyspepsia (QOLRAD) questionnaires were sent to these patients in December 2004. The two groups were compared for each item nonparametrically. Results Completed questionnaires were received from 161 patients (61%) of whom 99 had a laparoscopic Nissen fundoplication and 62 laparoscopic Toupet fundoplication. Both procedures were equivalent in improving reflux symptom scores in the long term, 79/99 (80%) and 56/62 (90%) were either symptom free or had obtained significant symptomatic relief. Both groups had equivalent QoL scores on the QOLRAD questionnaire. An equivalent number of patients (86% and 83.9% after Nissen and Toupet, respectively) were sufficiently satisfied to recommend antireflux surgery to a friend or relative complaining of reflux symptoms. Conclusion In conclusion, in patients who have returned the questionnaire, long-term satisfaction, general symptom scores, and quality of life are equivalent after laparoscopic Nissen (complete) or Toupet (partial) fundoplication. There is however, a significant increased prevalence of persistent heartburn after laparoscopic Toupet fundoplication.  相似文献   
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Metatarsal sprains of Chopart’s joint are less well known than those of the talocrural joint. A correctly performed, specific standard X-ray, guided by clinical examination, is usually sufficient to assess the injury. We present an exceptional case of a pure bilateral sprain of the mediotarsal joint, in a young woman aged 25, caused by a poor landing after a jump. The clinical exam guided diagnosis and the X-ray of the foot showed bilateral tearing of the upper talonavicular ligament, bearing witness to a severe sprain. Functional treatment was adopted, consisting of wearing orthotic footwear with special soles for six weeks. Additional functional rehabilitation was also implemented. The result was satisfactory with consolidation of the bone tear, recovery of mobility and the elimination of pain in the metatarsal joint.  相似文献   
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Echinococcosis is a widespread zoonosis which is endemic in most sheep-raising countries. Primary isolated muscular localisation is uncommon even in these endemic areas. The authors report a rare case of primary hydatid cyst localized in the myotendinous junction of the flexor digitorum profundus. According to our review of the medical literature, there are no reports of a similar case, making ours the first such report.  相似文献   
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Palliation of advanced esophageal cancer continues to be a challenge to clinicians. Self expanding metal stents have been used in the esophagus for palliation of advanced esophageal cancer since 1983. They are relatively easy to insert by practicing endoscopists and have low rates of early complications. Delayed complications necessitating reintervention can arise in as many as a third of patients. The majority of stents are placed under sedation using endoscopy and fluoroscopy. Once deployed, they expand in the esophagus causing pressure necrosis on the wall of the esophagus. Several stents are available on the market with newer designs continuing to emerge. Choice of stent seems random among clinicians. Stents have been used for the management of esophageal obstruction including cervical esophageal obstruction and obstruction at the esophagogastric junction, tracheopulmonary fistulae, and mediastinal esophageal compression. Complications include chest pain, deployment and expansion problems, stent migration, tumor overgrowth and ingrowth, gastroesophageal reflux, and stent-related hemorrhage. Despite their high cost, stenting produce better palliation and some cost savings in comparison to conventional methods of palliation. Combination therapy using stenting followed by chemo/radio therapy may increase quality survival.  相似文献   
49.
Several studies have demonstrated the role of free radicals in causing esophagus-gastro-duodenal mucosal injury. The present study has been designed to investigate: whether acid, bile salts and a combination of bile + acid could determine the production of O2-derived free radicals by oesophageal, gastric and duodenal mucosa; which agent is capable of producing more free radicals and if O2-derived free radicals production depends on the duration of contact with acid, bile salts and their combination. Wistar rats' gastro-intestinal mucosa were perfused with bile, acid and a combination of bile + acid at pH4 and pH2 for 1 hour and 2 hours. Free radical production (FRP) was assessed by chemoluminescence. After 1 hour, the increase in FRP in comparison with control reached statistical significance (P < 0.05) at all tested pH levels in the duodenum, at pH1, 2 and 3 in the esophagus, and at pH1 in the stomach. Comparing different segments, both the esophagus and duodenum behaved similarly, producing more free radicals than the stomach at all pH values. However, this difference reached statistical significance at pH1 and 2 only. In comparison to control, FRP was increased by bile (pH7) infusion after 1 and 2 hours. There was increased FRP in all segments after the infusion of bile at pH2 and 4 in comparison to control. Infusion of bile at pH2 stimulates more FRP than infusion of bile at pH4 in all segments. This increased FRP reaches statistical significance in the esophagus after 2 hours of infusion, in the stomach after 1 and 2 hours of infusion, but in the duodenum it does not reach statistical significance. Acid, bile and bile + acid at pH2 and 4 can cause free radical production in esophageal, gastric and duodenal mucosa. Their role in producing free radicals is different according to the segment and the chemical composition of the solution.  相似文献   
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