全文获取类型
收费全文 | 1808篇 |
免费 | 151篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 10篇 |
儿科学 | 64篇 |
妇产科学 | 24篇 |
基础医学 | 236篇 |
口腔科学 | 145篇 |
临床医学 | 146篇 |
内科学 | 381篇 |
皮肤病学 | 9篇 |
神经病学 | 133篇 |
特种医学 | 83篇 |
外科学 | 208篇 |
综合类 | 9篇 |
预防医学 | 161篇 |
眼科学 | 20篇 |
药学 | 155篇 |
中国医学 | 1篇 |
肿瘤学 | 179篇 |
出版年
2023年 | 7篇 |
2022年 | 10篇 |
2021年 | 28篇 |
2020年 | 23篇 |
2019年 | 30篇 |
2018年 | 52篇 |
2017年 | 43篇 |
2016年 | 49篇 |
2015年 | 56篇 |
2014年 | 93篇 |
2013年 | 112篇 |
2012年 | 125篇 |
2011年 | 144篇 |
2010年 | 99篇 |
2009年 | 82篇 |
2008年 | 115篇 |
2007年 | 123篇 |
2006年 | 102篇 |
2005年 | 103篇 |
2004年 | 73篇 |
2003年 | 79篇 |
2002年 | 60篇 |
2001年 | 45篇 |
2000年 | 39篇 |
1999年 | 31篇 |
1998年 | 24篇 |
1997年 | 18篇 |
1996年 | 8篇 |
1995年 | 10篇 |
1994年 | 5篇 |
1993年 | 11篇 |
1992年 | 15篇 |
1991年 | 9篇 |
1990年 | 13篇 |
1989年 | 15篇 |
1988年 | 4篇 |
1987年 | 14篇 |
1986年 | 11篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 10篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1979年 | 11篇 |
1973年 | 3篇 |
1968年 | 3篇 |
1966年 | 3篇 |
1964年 | 2篇 |
1963年 | 2篇 |
1961年 | 2篇 |
排序方式: 共有1964条查询结果,搜索用时 171 毫秒
81.
Kaposi sarcoma-associated herpesvirus in non-Hodgkin lymphoma and reactive lymphadenopathy in Uganda
Engels EA Mbulaiteye SM Othieno E Gomez M Mathew S Cesarman E Knowles DM Chadburn A 《Human pathology》2007,38(2):308-314
Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma and is also associated with primary effusion lymphoma, a subset of diffuse large B-cell lymphomas, and multicentric Castleman disease. Because KSHV infection is endemic in sub-Saharan Africa, we sought to identify cases of KSHV-positive non-Hodgkin lymphomas (NHLs) and reactive lymphadenopathy in this region. One hundred forty-four cases (80 NHLs, 64 reactive lymph nodes) from the major pathology laboratory in Uganda were reviewed. One NHL was KSHV-positive, as indicated by staining for the viral latent nuclear antigen. This NHL was a diffuse large B-cell lymphoma in a 5-year-old boy. The tumor was also Epstein-Barr virus-positive. In addition, 2 reactive lymph nodes, both classified histologically as follicular involution, stained KSHV latent nuclear antigen-positive and thus most likely represent multicentric Castleman disease. In all 3 KSHV-positive cases, a minority of cells expressed KSHV viral interleukin 6, a biologically active cytokine homolog. In conclusion, we show that KSHV is rarely associated with lymphoproliferative disorders in sub-Saharan Africa. We describe the first case of a KSHV-positive NHL from this region; this case is also the first reported pediatric lymphoma associated with KSHV infection. 相似文献
82.
Dynamic intracellular survivin in oral squamous cell carcinoma: underlying molecular mechanism and potential as an early prognostic marker 总被引:7,自引:0,他引:7
Engels K Knauer SK Metzler D Simf C Struschka O Bier C Mann W Kovács AF Stauber RH 《The Journal of pathology》2007,211(5):532-540
Survivin functions as an apoptosis inhibitor and a regulator of cell division in many tumours. The intracellular localization of survivin in tumours has been suggested as a prognostic marker. However, current reports are inconsistent and the underlying molecular mechanisms are not understood. The present study has examined the localization and prognostic value of nuclear and cytoplasmic survivin in the pre-therapeutic biopsies from 71 oral and oropharyngeal squamous carcinoma (OSCC) patients. Statistical analysis indicated that preferential nuclear versus cytoplasmic survivin correlated with favourable versus unfavourable disease outcome. Uni- and multi-variate analysis showed that in contrast to total survivin expression, the difference between nuclear and cytoplasmic survivin was a strong predictor for relapse-free survival (p=0.0003). As a potential underlying molecular mechanism, it is shown in OSCC cell lines that predominantly cytoplasmic survivin mediates protection against chemo- and radio-therapy-induced apoptosis. Importantly, the cytoplasmic localization of survivin is regulated by its nuclear export signal (NES), and export-deficient nuclear survivin is not cytoprotective. This study suggests that the difference between cytoplasmic and nuclear survivin is an indicator for survivin activity in tumour cells. Thus, this difference may serve as a predictive marker of outcome in OSCC patients undergoing multi-modality therapy. The pharmacogenetic interference with survivin's cytoplasmic localization is also to be pursued as a potential therapeutic strategy. 相似文献
83.
Some 90% of oral cancers consist of squamous cell carcinomas that arise from the oral mucosa. The remaining 10% of malignancies consist of malignant melanomas, carcinomas of the intraoral salivary glands, sarcomas of the soft tissues and the bones, malignant odontogenic tumors, non-Hodgkin's lymphomas and metastases from primary tumors located elsewhere in the body. These malignancies will be briefly reviewed and discussed. The emphasis is on diagnosis and management. 相似文献
84.
Rutger C. Lalieu Robin J. Brouwer Dirk T. Ubbink Rigo Hoencamp Ren Bol Raap Rob A. van Hulst 《Wound repair and regeneration》2020,28(2):266-275
Diabetic foot ulcers are a common complication of diabetes, which affects 25% of patients and may ultimately lead to amputation of affected limbs. Research suggests hyperbaric oxygen therapy improves healing of these ulcers. However, this has not been reflected in previous reviews, possibly because they did not differentiate between patients with and without peripheral arterial occlusive disease. Therefore, we performed a systematic review of published literature in the MEDLINE, Embase, and Cochrane CENTRAL databases on nonischemic diabetic foot ulcers with outcome measures including complete ulcer healing, amputation rate (major and minor), and mortality. Seven studies were included, of which two were randomized clinical trials. Two studies found no difference in major amputation rate, whereas one large retrospective study found 2% more major amputations in the hyperbaric oxygen group. However, this study did not correct for baseline differences. Two studies showed no significant difference in minor amputation rate. Five studies reporting on complete wound healing showed no significant differences. In conclusion, the current evidence suggests that hyperbaric oxygen therapy does not accelerate wound healing and does not prevent major or minor amputations in patients with a diabetic foot ulcer without peripheral arterial occlusive disease. Based on the available evidence, routine clinical use of this therapy cannot be recommended. However, the available research for this specific subgroup of patients is scarce, and physicians should counsel patients on expected risks and benefits. Additional research, focusing especially on patient selection criteria, is needed to better identify patients that might profit from this therapy modality. 相似文献
85.
This study examined whether personality traits and peer drinking affect alcohol consumption in young adults. Data were analyzed from a study that was conducted in a 'bar laboratory' in which ad-lib drinking of peer groups was observed. The findings indicate that extroversion is moderately associated with self-reported daily drinking, while low emotional stability is modestly associated with alcohol-related problems. With regard to drinking in the observational drinking setting, personality is not associated with young adults' actual alcohol consumption. Further, peer drinking levels were strongly related to young adults' drinking. Besides, agreeableness interacted with the effects of peer drinking on young adults' drinking in such a way that agreeable individuals adapted their actual alcohol consumption more easily than others when socializing in a high- or a low-drinking peer group. We concluded that drinking in a peer context, irrespective of personality, played a major role in forming young adults' drinking. However, personality (i.e. agreeableness) definitely played a role to the extent of the individuals' adaptation to peer drinking norms. 相似文献
86.
Peter J. Boon Godefridus I. Tesser Rutger J. F. Nivard 《Proceedings of the National Academy of Sciences of the United States of America》1979,76(1):61-65
Horse heart cytochrome c was treated with methylsulfonylethyloxycarbonyl succinimide (Msc-ONSu) to give fully N(epsilon)-protected cytochrome c. Treatment of this derivative with a hard base for 15 sec regenerated the native tetrahectapeptide chain. CNBr degradation of the protected compound produced three fragments bearing only protective Msc functions on epsilon-amino groups. The fragment comprising the sequence 81-104 was isolated from the mixture and acylated with N-hydroxysuccinimidyl-t-butyloxycarbonyl-L-methioninate. The resulting pentacosapeptide derivative was partially deprotected by treatment with acid and condensed in good yield (65%) with fully synthetic N(alpha66), N(epsilon72,73,79)- tetra-Msc-cytochrome-c-(66-79)-tetradecapeptide azide. This pathway is preferred because the pentadecapeptide azide derivative 66-80 acylated the N(epsilon)-protected tetracosapeptide sequence 81-104 in an unpredictable manner. Subsequent treatment of the product with a base produced unprotected semisynthetic cytochrome-c-(66-104)-nonatriacontapeptide, which is known to undergo acylation by unprotected [Hse(65)]cytochrome-c-(1-65)-pentahexacontapeptide lactone. The high specificity of this condensation is ascribed to "conformation direction." Semisynthetic [Hse(65)]cytochrome c thus prepared reacts like native cytochrome c with a succinate cytochrome c reductase preparation and with cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). This semisynthetic strategy may provide a rapid route for the production of cytochrome c analogs modified in the highly conservative sequence 66-80. 相似文献
87.
Inge L. W. Bastiaanssen Marc J. M. H. Delsing Luuk Geijsen Gert Kroes Jan W. Veerman Rutger C. M. E. Engels 《Child & youth care forum》2014,43(2):227-241
Background
The work of group care workers in residential youth care is often described as professional parenting. Pedagogical interventions of group care workers influence the quality of care for looked-after children.Objective
The aim of the current study was to observe the pedagogical interventions of group care workers within residential youth care and their associations with child behaviors.Methods
Group care worker interventions and child behaviors were videotaped during structured observations. Participants included 95 children (64 % boys, M age = 9.19) and 53 group care workers (74 % female, M age = 33.79 years). A coding system was developed to code pedagogical interventions and child behaviors.Results
It showed that group care workers mainly used positive pedagogical interventions (warmth/support and positive control) and seldom used negative pedagogical interventions (permissiveness and negative control). Frustration and anger of children was associated with positive controlling interventions and permissiveness of group care workers. The hypothesis that child anxiety and nervousness is associated with warm and supportive interventions could not be confirmed.Conclusions
Pedagogical interventions should be part of education, training, and supervision of group care workers. 相似文献88.
Eugene F. Diekman W. Ludo van der Pol Rutger A. J. Nievelstein Sander M. Houten Frits A. Wijburg Gepke Visser 《Journal of inherited metabolic disease》2014,37(3):405-413
Introduction
Muscle magnetic resonance imaging (MRI) is a useful tool for visualizing abnormalities in neuromuscular disorders. The value of muscle MRI has not been studied in long-chain fatty acid oxidation (lcFAO) disorders. LcFAO disorders may present with metabolic myopathy including episodic rhabdomyolysis.Objective
To investigate whether lcFAO disorders are associated with muscle MRI abnormalities.Methods
Lower body MRI was performed in 20 patients with lcFAO disorders, i.e. three carnitine palmitoyltransferase 2 deficiency (CPT2D), 12 very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), three mitochondrial trifunctional protein deficiency (MTPD) and two isolated long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD).Results
At the time of MRI, four patients had muscle weakness, 14 had muscle pain and 13 were exercise intolerant. Median creatine kinase (CK) level of patients at the day of MRI was 398 U/L (range 35-12,483). T1W and STIR signal intensity (SI) were markedly increased in MTPD patients from girdle to lower leg. VLCADD patients showed predominantly proximal T1W SI changes, whereas LCHADD patients mostly showed distal T1W SI changes. Prominent STIR weighted signal intensity increases of almost all muscle groups were observed in patients with VLCADD and LCHADD with very high CK (>11.000) levels.Conclusions and relevance
lcFAO disorders are associated with specific patterns of increased T1W and STIR signal intensity. These patterns may reflect lipid accumulation and inflammation secondary to lcFAO defects and progressive muscle damage. Future studies are needed to investigate whether muscle MRI might be a useful tool to monitor disease course and to study pathogenesis of lcFAO related myopathy. 相似文献89.
Yoko Nakajima Judith Meijer Doreen Dobritzsch Tetsuya Ito Rutger Meinsma Nico G. G. M. Abeling Jeroen Roelofsen Lida Zoetekouw Yoriko Watanabe Kyoko Tashiro Tomoko Lee Yasuhiro Takeshima Hiroshi Mitsubuchi Akira Yoneyama Kazuhide Ohta Kaoru Eto Kayoko Saito Tomiko Kuhara André B. P. van Kuilenburg 《Journal of inherited metabolic disease》2014,37(5):801-812
β-ureidopropionase (βUP) deficiency is an autosomal recessive disease characterized by N-carbamyl-β-amino aciduria. To date, only 16 genetically confirmed patients with βUP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese βUP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant βUP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (≤ 1.3 %). Conversely, βUP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human βUP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that βUP deficiency is not as rare as generally considered and screening for βUP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities. 相似文献
90.
Bone marrow 18F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography/computed tomography cannot replace bone marrow biopsy in diffuse large B‐cell lymphoma 下载免费PDF全文
Hugo J.A. Adams Thomas C. Kwee Rob Fijnheer Stefan V. Dubois Rutger A.J. Nievelstein John M.H. de Klerk 《American journal of hematology》2014,89(7):726-731
This study aimed to investigate whether visual and quantitative 18F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography/computed tomography (FDG‐PET/CT)‐based bone marrow assessment can replace blind bone marrow biopsy (BMB) in newly diagnosed diffuse large B‐cell lymphoma (DLBCL). This retrospective study included 78 patients with newly diagnosed DLBCL who had undergone both FDG‐PET/CT and BMB. FDG‐PET/CT images were visually evaluated for bone marrow involvement. Patient‐based sensitivity of visual FDG‐PET/CT assessment was calculated using BMB as the reference standard. Metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, and 3D partial volume corrected mean metabolic volume product (cMVPmean) of FDG‐avid bone marrow lesions were measured. Cox regression analysis was used to determine the influence of (potential) prognostic factors (BMB status, visual [dichotomous] FDG‐PET/CT bone marrow status, metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, 3D partial volume corrected mean metabolic volume product, and International Prognostic Index score) on progression‐free survival and overall survival. FDG‐PET/CT detected bone marrow involvement in 34 (43.6%) cases and BMB in 16 (20.5%) of 78 cases, of whom 11 were also detected by FDG‐PET/CT, resulting in a patient‐based sensitivity of 68.8% (95% confidence interval = 44.2%–86.1%) for FDG‐PET/CT. In the multivariate Cox proportional hazards model, only BMB status was an independent predictive factor of progression‐free survival (P = 0.016) and overall survival (P = 0.004). In conclusion, FDG‐PET/CT misses bone marrow involvement that has been detected by BMB in a non‐negligible proportion of patients. Furthermore, both visual and quantitative FDG‐PET/CT‐based bone marrow assessments are prognostically inferior to BMB. Therefore, FDG‐PET/CT cannot replace BMB in newly diagnosed DLBCL. Am. J. Hematol. 89:726–731, 2014. © 2014 Wiley Periodicals, Inc. 相似文献