全文获取类型
收费全文 | 851篇 |
免费 | 46篇 |
国内免费 | 12篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 87篇 |
妇产科学 | 16篇 |
基础医学 | 118篇 |
口腔科学 | 27篇 |
临床医学 | 61篇 |
内科学 | 90篇 |
皮肤病学 | 10篇 |
神经病学 | 22篇 |
特种医学 | 8篇 |
外科学 | 36篇 |
综合类 | 66篇 |
预防医学 | 219篇 |
眼科学 | 1篇 |
药学 | 57篇 |
中国医学 | 3篇 |
肿瘤学 | 84篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 18篇 |
2021年 | 19篇 |
2020年 | 25篇 |
2019年 | 57篇 |
2018年 | 58篇 |
2017年 | 46篇 |
2016年 | 27篇 |
2015年 | 44篇 |
2014年 | 78篇 |
2013年 | 68篇 |
2012年 | 50篇 |
2011年 | 63篇 |
2010年 | 47篇 |
2009年 | 48篇 |
2008年 | 52篇 |
2007年 | 43篇 |
2006年 | 32篇 |
2005年 | 33篇 |
2004年 | 14篇 |
2003年 | 16篇 |
2002年 | 9篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有909条查询结果,搜索用时 31 毫秒
91.
R. Constance Wiener Chan Shen Patricia A. Findley Usha Sambamoorthi Xi Tan 《Journal of the American Dental Association (1939)》2017,148(7):500-509.e4
Background
Sugar-sweetened beverages (SSBs) are dietary sources of sugar that are factors in caries development and tooth loss. Dietary sugar also is linked to diabetes mellitus (DM). There is limited research related to SSBs and tooth loss in people with DM. The authors investigated the association between SSBs and tooth loss as it related to the presence or absence of DM.Methods
The authors used a cross-sectional design with data reported by adults (18 years and older) who responded to the 2012 Behavior Risk Factor Surveillance System questionnaire, which was used in 18 states (N = 95,897; 14,043 who had DM and 81,854 who did not have DM). The authors conducted χ2 and logistic regression analyses to determine associations related to DM status.Results
Overall, 12.3% of the survey respondents had DM, 15.5% had 6 or more teeth extracted, and 22.6% reported that they consumed 1 or more SSB daily. In the adjusted analyses, among adults who had DM, those who consumed at least 2 SSBs daily were more likely to have had 6 or more teeth extracted than those who reported that they did not consume SSBs (adjusted odds ratio, 2.35; 95% confidence interval, 1.37 to 4.01; P = .0018). Among adults who did not have DM, those who consumed more than 1 but fewer than 2 SSBs per day were more likely to have had at least 6 teeth extracted (adjusted odds ratio, 1.46; 95% confidence interval, 1.21 to 1.77; P < .0001).Conclusions
The authors found that, among adults with DM, consuming 2 or more SSBs per day was associated with having had 6 or more teeth extracted.Practical Implications
Dietary sugar is a concern for oral and systemic health; however, a strong, independent relationship between the number of teeth extracted and a single source of dietary sugar is not adequate to explain the complexity of tooth loss. Clinicians should use broadly worded dietary messages when discussing caries assessment with patients. 相似文献92.
Cameron G. Estrich Stephen E. Gruninger Ruth D. Lipman 《Journal of the American Dental Association (1939)》2017,148(3):164-171
Background
In this study, the authors compared the odds of exposure to Legionella pneumophila among currently active dental practitioners with that of nonpractitioners and evaluated demographic and clinical practice predictors of exposure.Methods
The authors obtained demographic characteristics and dental practice behaviors from participants in the annual American Dental Association Health Screening Program survey administered from 2002 through 2012. The authors assayed serum samples obtained from participants for L pneumophila antibodies. The authors used an adjusted logit model to evaluate predictors of positive results.Results
Among 5,431 participants, approximately 10% were positive for L pneumophila, with no significant differences between dental practitioners and nonpractitioners. Geographic location was the only significant predictor of seropositivity, with no increased risk of being exposed to L pneumophila associated with age, race, sex, years in practice, hours of practice per week, use of barrier protection, or infection control practices.Conclusions
Prevalence of L pneumophila antibodies was 10.4% among dental and nondental personnel. US Census division was the only significant predictor of seropositivity. The authors conclude that provision of dental care did not increase the risk of being exposed to Legionella.Practical Implications
Dentists should be aware of the prevalence of Legionella species in their practice areas to understand their personal risk of developing an infection. 相似文献93.
Mark W. Lingen Malavika P. Tampi Olivia Urquhart Elliot Abt Nishant Agrawal Anil K. Chaturvedi Ezra Cohen Gypsyamber D’Souza JoAnn Gurenlian John R. Kalmar Alexander R. Kerr Paul M. Lambert Lauren L. Patton Thomas P. Sollecito Edmond Truelove Laura Banfield Alonso Carrasco-Labra 《Journal of the American Dental Association (1939)》2017,148(11):797-813.e52
Background
Oral squamous cell carcinoma is the most common manifestation of malignancy in the oral cavity. Adjuncts are available for clinicians to evaluate lesions that seem potentially malignant. In this systematic review, the authors summarized the available evidence on patient-important outcomes, diagnostic test accuracy (DTA), and patients’ values and preferences (PVPs) when using adjuncts for the evaluation of clinically evident lesions in the oral cavity.Types of Studies Reviewed
The authors searched for preexisting systematic reviews and assessed their quality using the Assessing the Methodological Quality of Systematic Reviews tool. The authors updated the selected reviews and searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials and DTA and PVPs studies. Pairs of reviewers independently conducted study selection, data extraction, and assessment of the certainty in the evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach.Results
The authors identified 4 existing reviews. DTA reviews included 37 studies. The authors retrieved 7,534 records, of which 9 DTA and 10 PVPs studies were eligible. Pooled sensitivity and specificity of adjuncts ranged from 0.39 to 0.96 for the evaluation of innocuous lesions and from 0.31 to 0.95 for the evaluation of suspicious lesions. Cytologic testing used in suspicious lesions appears to have the highest accuracy among adjuncts (sensitivity, 0.92; 95% confidence interval, 0.86 to 0.98; specificity, 0.94; 95% confidence interval, 0.88 to 0.99; low-quality evidence).Conclusions and Practical Implications
Cytologic testing appears to be the most accurate adjunct among those included in this review. The main concerns are the high rate of false-positive results and serious issues of risk of bias and indirectness of the evidence. Clinicians should remain skeptical about the potential benefit of any adjunct in clinical practice. 相似文献94.
目的分析北京协和医院儿童/青少年散发性原发性甲状旁腺功能亢进症(PHPT)的临床特点和基因遗传背景,探索CDC73基因突变对此类患者临床特点的影响。方法总结2000-2016年就诊于北京协和医院的22例儿童/青少年散发性PHPT的临床资料;提取外周血白细胞DNA,进行MEN1、RET、CDKN1B、CDC73和Ca SR基因的PCR扩增及测序。结果 22例中检测到4例CDC73基因突变(突变率18.0%),未发现上述其他致病基因突变;CDC73突变患者中腺癌和不典型腺瘤所占比例分别为75%(3/4)和25%(1/4),明显高于无突变者(6.3%和12.5%),术后复发率高达50%。结论儿童/青少年PHPT应重视基因检测。 相似文献
95.
Marieke H. Heineke Aranka V. Ballering Agnès Jamin Sanae Ben Mkaddem Renato C. Monteiro Marjolein Van Egmond 《Autoimmunity reviews》2017,16(12):1246-1253
Immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, is the most common form of childhood vasculitis. The pathogenesis of IgAV is still largely unknown. The disease is characterized by IgA1-immune deposits, complement factors and neutrophil infiltration, which is accompanied with vascular inflammation. Incidence of IgAV is twice as high during fall and winter, suggesting an environmental trigger associated to climate. Symptoms can resolve without intervention, but some patients develop glomerulonephritis with features similar to IgA nephropathy that include hematuria, proteinuria and IgA deposition in the glomerulus. Ultimately, this can lead to end-stage renal disease. In IgA nephropathy immune complexes containing galactose-deficient (Gd-)IgA1 are found and thought to play a role in pathogenesis. Although Gd-IgA1 complexes are also present in patients with IgAV with nephritis, their role in IgAV is disputed. Alternatively, it has been proposed that in IgAV IgA1 antibodies are generated against endothelial cells. We anticipate that such IgA complexes can activate neutrophils via the IgA Fc receptor FcαRI (CD89), thereby inducing neutrophil migration and activation, which ultimately causes tissue damage in IgAV. In this Review, we discuss the putative role of IgA, IgA receptors, neutrophils and other factors such as infections, genetics and the complement system in the pathogenesis of IgA vasculitis. 相似文献
96.
Jayendra Kumar Krishnaswamy Arpita Singh Uthaman Gowthaman Renee Wu Pavane Gorrepati Manuela Sales Nascimento Antonia Gallman Dong Liu Anne Marie Rhebergen Samuele Calabro Lan Xu Patricia Ranney Anuj Srivastava Matthew Ranson James D. Gorham Zachary McCaw Steven R. Kleeberger Leonhard X. Heinz André C. Müller Keiryn L. Bennett Giulio Superti-Furga Jorge Henao-Mejia Fayyaz S. Sutterwala Adam Williams Richard A. Flavell Stephanie C. Eisenbarth 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(10):3056-3061
Dendritic cells (DCs) are the primary leukocytes responsible for priming T cells. To find and activate naïve T cells, DCs must migrate to lymph nodes, yet the cellular programs responsible for this key step remain unclear. DC migration to lymph nodes and the subsequent T-cell response are disrupted in a mouse we recently described lacking the NOD-like receptor NLRP10 (NLR family, pyrin domain containing 10); however, the mechanism by which this pattern recognition receptor governs DC migration remained unknown. Using a proteomic approach, we discovered that DCs from Nlrp10 knockout mice lack the guanine nucleotide exchange factor DOCK8 (dedicator of cytokinesis 8), which regulates cytoskeleton dynamics in multiple leukocyte populations; in humans, loss-of-function mutations in Dock8 result in severe immunodeficiency. Surprisingly, Nlrp10 knockout mice crossed to other backgrounds had normal DOCK8 expression. This suggested that the original Nlrp10 knockout strain harbored an unexpected mutation in Dock8, which was confirmed using whole-exome sequencing. Consistent with our original report, NLRP3 inflammasome activation remained unaltered in NLRP10-deficient DCs even after restoring DOCK8 function; however, these DCs recovered the ability to migrate. Isolated loss of DOCK8 via targeted deletion confirmed its absolute requirement for DC migration. Because mutations in Dock genes have been discovered in other mouse lines, we analyzed the diversity of Dock8 across different murine strains and found that C3H/HeJ mice also harbor a Dock8 mutation that partially impairs DC migration. We conclude that DOCK8 is an important regulator of DC migration during an immune response and is prone to mutations that disrupt its crucial function.Dendritic cells (DCs) are crucial for the initiation of an adaptive immune response. Upon acquiring antigens in the periphery, DCs undergo a maturation process that includes antigen processing, cytokine production, and up-regulation of costimulatory molecules. A mature DC must then migrate from peripheral tissues to draining lymph nodes (LNs) to fulfill its role as an antigen-presenting cell that primes naïve T cells (1). Although the signals that induce this maturation process are now well-established (1), relatively little is understood about DC migration aside from the primary chemotactic cue provided by CCR7 that guides DCs to the LN (2, 3).We recently described a genetically modified NLRP10 (NLR family, pyrin domain containing 10) knockout strain in which this migration step was disrupted while leaving the remainder of the DC maturation program, including CCR7 expression, intact (4). NLRP10 is the only NOD-like receptor (NLR) without a leucine-rich repeat domain, the putative pathogen-associated molecular pattern (PAMP)–binding domain. It has been proposed to both positively and negatively regulate other NLRs, such as NOD1 and NLRP3, respectively (5, 6). Although we found that NLRP3 inflammasome activation was unaltered in the absence of NLRP10, we discovered that Nlrp10−/− mice could not mount a productive T- or B-cell immune response due to a DC-intrinsic failure to emigrate out of inflamed tissues (4, 7).To understand the mechanism by which NLRP10 governs DC migration, we used an expression proteomic approach to identify molecules with altered expression in DCs generated from the Nlrp10−/− strain and discovered a profound reduction in DOCK8 (dedicator of cytokinesis 8). DOCK8 is a guanine nucleotide exchange factor (GEF) that has two functional domains, DOCK homology region (DHR) 1 and DHR2 (8). In murine DCs, the DHR2 domain has been implicated in regulating the Rho GTPase CDC42 (cell division control protein 42 homolog), which in turn maintains cell polarity of mature DCs during migration (9, 10). Furthermore, mice harboring inactivating mutations in Dock8 lack marginal zone B-cell development, long-term antibody production following immunization, and memory CD8+ T-cell responses to viral infections (11, 12). In humans, inactivating mutations in Dock8 were recently identified as the primary genetic cause underlying autosomal recessive hyper-IgE syndrome (13). This syndrome presents with eczema, recurrent infections of the skin and respiratory tract, increased serum IgE, eosinophilia, recurrent fungal and viral infections, extensive food and environmental allergies, and, in certain patients, squamous cell dysplasia and carcinomas (14).Given that DOCK8 regulates a wide array of immunologic processes in mouse and human, we sought to understand how NLRP10 regulates DOCK8. To our surprise, we discovered that loss of DOCK8 in the Nlrp10−/− strain was secondary to a point mutation within the Dock8 gene itself. In this study, we demonstrate that restoring DOCK8 function in the Nlrp10−/− strain leads to normal DC migration in vivo. We further show that deletion of Dock8, as well as spontaneous mutation of Dock8 in another inbred strain of mice, results in defective DC migration and, depending on the degree of impaired migration, also abrogates CD4+ T-cell activation. 相似文献
97.
A novel coumarin‐quinone derivative SV37 inhibits CDC25 phosphatases,impairs proliferation,and induces cell death 下载免费PDF全文
98.
Kyu Ha Huh Myoung Soo Kim Hae Jin Kim Dong Jin Joo Beom Seok Kim Man Ki Ju Soon Il Kim Yu Seun Kim 《Transplant international》2012,25(11):1131-1137
Recently, Luminex‐crossmatch (LumXm) was introduced. The aim of this study was to evaluate clinical outcomes in sensitized recipients with a positive Luminex‐crossmatch (LumXm (+)) and a negative complement‐dependent cytotoxicity crossmatch (CDCXm (?)) after renal transplantation. Fifty‐five renal transplant recipients with a CDCXm (?) and PRA class I or II ≥20% were enrolled in this study between February 2008 and December 2010 at Severance Hospital. Eighteen patients displayed LumXm (+) defined as LumXm positive class I or II and 37 patients displayed LumXm (?). Mean duration of follow‐up was 18.9 ± 8.3 months. During this period, no patient death or graft loss occurred. The incidence of biopsy‐proven or clinically presumed rejection was higher in the LumXm (+) group (n = 12, 66.7%) than in the LumXm (?) group (n = 6, 18.2%) (P = 0.001). All biopsy‐proven acute rejections (n = 12) were diagnosed as acute cellular rejection. No significant difference in mean serum creatinine level or eGFR was observed between the groups at 18 months post‐transplantation. The short‐term outcome of renal transplantation in sensitized patients with a LumXm (+) and a CDCXm (?) may be considered to be acceptable. However, patients with a LumXm (+) have a substantially higher immunological risk for the development of acute cellular rejection. 相似文献
99.
Stanberry LR Simon JK Johnson C Robinson PL Morry J Flack MR Gracon S Myc A Hamouda T Baker JR 《Vaccine》2012,30(2):307-316
Background
Improving the systemic and mucosal immune response following intranasal vaccination could enhance disease protection against respiratory pathogens. We assessed the safety and immunogenicity of a novel nanoemulsion mucosal adjuvant W805EC combined with approved seasonal influenza antigens.Methods
This was a first-in-human Phase I study in 199 healthy adult volunteers randomized to receive a single intranasal administration of 5%, 10%, 15% or 20% W805EC, combined with 4 or 10 μg strain-specific Fluzone® HA, compared with intranasal PBS, intranasal Fluzone®, or 15 ug strain-specific intramuscular Fluzone®. Safety was evaluated by physical examination, laboratory parameters, symptom diaries, and adverse event reports. Serum HAI titers and nasal wash IgA were assessed at baseline as well as 28 and 60 days after vaccination.Results
W805EC adjuvant combined with seasonal influenza antigens was well tolerated without safety concerns or significant adverse events. The highest dose of 20% W805EC combined with 10 μg strain-specific HA elicited clinically meaningful systemic immunity based on increases in serum HAI GMT and ≥70% seroprotection for all 3 influenza strains, as well as a rise in antigen-specific IgA in nasal wash specimens.Conclusions
W805EC adjuvant was safe and well tolerated in healthy adult volunteers and elicited both systemic and mucosal immunity following a single intranasal vaccination. 相似文献100.