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1.
With no known intervention to prevent or cure epilepsy, treatment is primarily symptomatic and requires long-term administration of medications to suppress seizure occurrence. Current antiepileptic drugs (AEDs) are ineffective in one-third of patients (Kwan and Brodie, 2000, [1]). Such therapeutic inadequacy is largely due to our insufficient understanding of the basic molecular pathophysiological processes that underlie epileptogenesis. Breakthroughs are needed in the identification of new molecular targets that will translate to novel intervention approaches.Discovering genetic variants that increase the susceptibility to disease is a promising avenue to identifying such targets. However, early candidate gene-based studies in epilepsy proved ineffective in identifying genetic risk factors for the non-Mendelian, complex epilepsies, which represent > 95% of clinically encountered epilepsy. Furthermore, genome-wide association studies (GWAS) of epilepsy patients have been largely negative, with the exception of several putative susceptibility loci discovered in Han Chinese focal epilepsy and European Caucasian GGE patients (Kasperaviciute et al., 2010; Guo et al., 2012; Consortium et al., 2012, [2], [3], [4]). Results of these GWAS suggest that, similar to other common diseases, associations with common single nucleotide variants (SNV) appear likely to account for a small fraction of the heritability of epilepsy, thus fuelling the effort to also search for alternative genetic contributors, with a recent increased emphasis on rare variants with larger effects (Manolio et al., 2009, [5]).It is possible that both common and rare variants contribute to an increased susceptibility to common epilepsy syndromes (Mulley et al., 2005, [6]). We review the approaches that have been taken to identify genetic risk markers of the common epilepsy syndromes, the experimental platforms, and their caveats. We discuss current technologies and analytical frameworks that might expedite the discovery of these variants by leveraging advances in microarray-based, high-throughput, genotyping technology, and complementary interdisciplinary expertise of study teams including the need for meta-analyses under global collaborative frameworks. We briefly discuss the analytical options made available through rapid advances in sequencing and other genomic technologies.This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”. 相似文献
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Milenković S Mitković M Radenković M 《Vojnosanitetski pregled. Military-medical and pharmaceutical review》2005,62(1):11-15
AIM: To present the possibility of a succesfful use of external skelatal fixation in treating the open and closed tibial shaft fractures with Mitkovi?'s external fixator. METHODS: External fixation was used in 115 patients with 118 fresh tibial shaft fractures, 82 males (71.3%) and 33 females (28.7%), average age 43.92 years (16-84). Open tibial shaft fractures were present in 37 (31.36%). All the fractures were treated with Mitkovi?'s external fixator type M 20. RESULTS: The results of external fixation were excellent or good in 94.07% of the cases, and bad in 5.08%. Pin tract infection appeared in 7 (5.93%) patients. In only 3 cases an external fixator was removed and treatment continued with the functional braces. Nonunion occurred in 6 (5.08%) patients, of which 4 were with open fractures (2 Gustilo type IIIB, 1 Gustilo type IIIA, 1 Gustilo type II) and 2 with the segment fractures. Compartment syndrome was observed in 1 (0.85%) patient with closed fracture. Malunion was found in 2 (1.69%) patients. CONCLUSION: External fixation of tibial shaft fractures is a simple and effective method to enable the safe healing of fractures, early mobilization of the patients, early weight-bearing, as well as early rehabilitation. Fixation of tibial shaft fractures was unilateral with convergent pins orientation, and there was also a possibility of compression and distraction. 相似文献
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Stanković N Ignjatović M Nozić D Hajduković Z 《Vojnosanitetski pregled. Military-medical and pharmaceutical review》2005,62(3):175-179
BACKGROUND: Postoperative recurrence of the liver hydatid disease befalls approximately 10-30% of patients. Preoperative or postoperative therapy with albendazole in single therapeutic protocol (800 mg/d, within 28 days) indicated the need to evaluate the hydatid cyst liquid protoscoleces viability. Morphological changes of protoscoleces following the treatment with drugs are not well known. AIM: To estimate the viability of protoscoleces after preoperative or postoperative albendazole therapy, and their ability for cystic metamorphosis. METHODS: A prospective, randomized clinical trial included 30 patients with liver hydatid disease, treated with albendazole and surgically (I group), and 30 patients in the control group treated only surgically (II group). The concentration of albendazole and its active metabolite albendazole sulphoxide in the cysts contents were determined using HPLC. Estimation of protoscoleces viability was based on the established micromorphologic criteria, and compared between the patients treated with albendazole, and the patients treated only surgically. Biological assessment of the viability was performed on protoscoleces with uncertain signs of the disturbed viability (unchanged structure, evaginated, without movements) using intraperitoneal injection of 1 ml of protoscoleces prepared suspension to AO type of rats. RESULTS: The concentration of albendazole in cysts' contents ranged from 0 to 64.9 microg/ml, and of its active metabolite from 0.5 to 40.8 microg/ml. The presence of fully viabile protoscoleces in the albendazol treated patients was significantly lower than in the control group. A significant difference was noticed in the presence of disintegrated protoscoleces without movements in the albendazol treated group, compared to the control group. Biological assessment of the viability showed incapability of these protoscoleces for cystic metamorphoses. CONCLUSION: Low viability of parasites due to medicamentous therapy is very useful and important to surgeons, because the fertility of cysts is lower, and the risk of the disease recurrence is reduced. 相似文献