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1.
The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing. 相似文献
2.
We describe herein the rare case of a hydatid cyst found in the breast of a 26-year-old woman. Clinically, the mass was at
first suspected of being a fibroadenoma, but fine needle aspiration cytology (FNAC) yielded clear fluid only. Histopathologic
examination of the resected speciman confirmed that it was a hydatid cyst. 相似文献
3.
R J Harrison P T Klouda D L Easty M Manku J Charles C M Stewart 《The British journal of ophthalmology》1989,73(10):816-822
Sixty-seven patients with keratoconus were classified according to atopic status. Keratoconus patients with and without atopy did not differ significantly with regard to sex, age of onset, or rate of keratoplasty, but patients with very high IgE levels were more prone to graft rejection. Atopy was less common in patients with unilateral keratoconus, and keratoconus occurred more frequently on the side of the dominant hand. There was a significantly lower frequency of HLA B7 in the keratoconus group than in the controls. No abnormalities of essential fatty acid metabolism were found in keratoconus patients with or without atopy. There was no social class bias in the group. The study included a brother and sister with keratoconus and atopy, and a non-atopic patient whose identical twin did not have keratoconus. 相似文献
4.
Administration of doses of linoleic acid (LA) up to 36 g/d in humans raised blood levels of linoleic acid but not of its metabolites. This is probably because the conversion of LA to gamma-linolenic acid (GLA) is slow and rate-limiting. We have found that administration of relatively small amounts of GLA, up to 360 mg/d, raises human blood levels of dihomogammalinolenic acid (DGLA) and arachidonic acid (AA). 相似文献
5.
I Singh M Maharjan D K Gautam R Mehar G Gathwala 《Kathmandu University Medical Journal》2006,4(4):506-509
Two rare cases of Waardenburg type II are reported. First case had three main features of WS-profound SN hearing loss, hetrochromia iris and white forelock of hair. Second case had moderate SNHL and depigmentation of hair. Key words: Hetrochromia iris, white forelock hair. 相似文献
6.
Gaurav Khanna Pankaj Pathak Vaishali Suri Mehar Chand Sharma Sujata Chaturvedi Arvind Ahuja M. Bhardwaj Ajay Garg Chitra Sarkar Rajeev Sharma 《Pathology, research and practice》2018,214(5):679-685
Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup. 相似文献
7.
Intracranial interhemispheric osteochondrolipoma: Diagnostic and surgical challenges in an extremely rare entity 下载免费PDF全文
Madhu Rajeshwari Vaishali Suri Kavneet Kaur Ashish Suri Ajay Garg Mehar Chand Sharma Chitra Sarkar 《Neuropathology》2016,36(5):470-474
Intracranial lipomas are rare developmental lesions, predominantly occurring in the interhemispheric location. Osteochondrolipoma is an extremely rare variant of lipoma with osseous and chondroid differentiation. We present a case of interhemispheric osteochondrolipoma, in a 2.5‐years‐old male child which was detected antenatally, in association with corpus callosum agenesis. The lesion progressively increased in size with resulting compression of surrounding structures, and was subjected to microsurgical decompression. To the best of our knowledge, this is the first case of intracranial interhemispheric osteochondrolipoma in the existing medical literature. Peculiarities of this case and the diagnostic and surgical challenges are discussed. 相似文献
8.
9.
Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population 总被引:1,自引:0,他引:1
Abubaker J Jehan Z Bavi P Sultana M Al-Harbi S Ibrahim M Al-Nuaim A Ahmed M Amin T Al-Fehaily M Al-Sanea O Al-Dayel F Uddin S Al-Kuraya KS 《The Journal of clinical endocrinology and metabolism》2008,93(2):611-618
CONTEXT: Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC. OBJECTIVE: The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC. DESIGN: We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes. RESULTS: PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs. CONCLUSION: A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways. 相似文献
10.
Mehar Naseem 《Toxicology mechanisms and methods》2014,24(7):512-519
Carbon tetrachloride (CCl4) is a highly toxic industrial solvent with pronounced systemic toxicity including brain. Neurotoxicity may be a direct result of hepatic dysfunction from CCl4 intoxication. Over the years CCl4 has been used as an excellent model for studying experimentally induced neurotoxicity in murine models. Hesperidin (HP) is a known cytoprotectant with comprehensive anti-oxidant and neuroprotective properties. The aim of the present study was to evaluate experimentally induced neurotoxicity by CCl4 and its abrogation by using antioxidant potential of HP. CCl4 caused a significant enhancement in the lipid peroxidation (LPO) levels and protein carbonyl (PC) content. HP supplementation significantly restored the LPO levels and PC content. It also replenished the altered enzymatic and non-enzymatic antioxidants in brain tissues of rats. The neurotoxicity markers were also restored to normalcy with HP treatment. It is suggested that HP, by attenuating neuronal oxidative stress, holds promise that can ameliorate CCl4-induced neurotoxicity. HP has the potential to be explored as a universal neuroprotectant in xenobiotically induced neurotoxicity mediated by oxidative stress. 相似文献