全文获取类型
收费全文 | 382篇 |
免费 | 24篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 29篇 |
妇产科学 | 1篇 |
基础医学 | 84篇 |
口腔科学 | 2篇 |
临床医学 | 14篇 |
内科学 | 85篇 |
皮肤病学 | 1篇 |
神经病学 | 52篇 |
特种医学 | 10篇 |
外科学 | 38篇 |
一般理论 | 1篇 |
预防医学 | 15篇 |
眼科学 | 3篇 |
药学 | 39篇 |
中国医学 | 1篇 |
肿瘤学 | 27篇 |
出版年
2024年 | 1篇 |
2023年 | 4篇 |
2022年 | 15篇 |
2021年 | 20篇 |
2020年 | 9篇 |
2019年 | 12篇 |
2018年 | 20篇 |
2017年 | 10篇 |
2016年 | 14篇 |
2015年 | 16篇 |
2014年 | 10篇 |
2013年 | 25篇 |
2012年 | 26篇 |
2011年 | 25篇 |
2010年 | 19篇 |
2009年 | 20篇 |
2008年 | 30篇 |
2007年 | 30篇 |
2006年 | 37篇 |
2005年 | 19篇 |
2004年 | 13篇 |
2003年 | 11篇 |
2002年 | 11篇 |
2001年 | 3篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1987年 | 1篇 |
排序方式: 共有408条查询结果,搜索用时 14 毫秒
41.
Echocardiographic and Biohumoral Characteristics in Patients With AL and TTR Amyloidosis at Diagnosis
下载免费PDF全文
![点击此处可从《Clinical cardiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Francesco Cappelli MD Samuele Baldasseroni MD Franco Bergesio MD Stefano Perlini MD Francesco Salinaro MD Luigi Padeletti MD Paola Attanà MD Alessandro Paoletti Perini MD Alberto Moggi Pignone MD Elisa Grifoni MD Alessia Fabbri MD Niccolò Marchionni MD Gian Franco Gensini MD Federico Perfetto MD 《Clinical cardiology》2015,38(2):69-75
42.
43.
44.
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
45.
Giuseppe Nanni Pietro Familiari Alessandro Mor Amerigo Iaconelli Vincenzo Perri Francesco Rubino Giuseppe Boldrini Maria Paola Salerno Laura Leccesi Samuele Iesari Liliana Sollazzi Valter Perilli Marco Castagneto Gertrude Mingrone Guido Costamagna 《Obesity surgery》2012,22(12):1897-1902
Background
The effectiveness of restrictive procedures has been inferior to that of malabsorbitive ones. Recent variants of restrictive procedures, i.e., gastric banding and sleeve gastrectomy, confirm the strive for more efficacious solutions with less complications. We investigated the balance between effectiveness and complications for a new restrictive procedure, a Transoral Endoscopic Vertical Gastroplasty (TOGa?)Methods
Seventy-nine morbidly obese patients were submitted to one out of three surgical procedures: TOGa? (29 patients), laparoscopic gastric bypass (LRYGBP; 20 patients), and biliopancreatic diversion (BPD; 30 patients). Mean BMI were 41.7 (35.4?C46.6), 44.8 (36.4?C54), and 47.5 (41?C60.3), respectively. All the patients reached a 2-year follow-up.Results
In TOGa? group BMI, respectively at 12 and 24?months, was 34.5 and 35.5, with 44 and 48.3?% of patients with BMI lower than 35. In LRYGBP group, BMI was 30.7 and 29.2?kg/m2, with 80 and 85?% of patients with BMI?<?35. In BPD group, BMI was 30 and 29.6?kg/m2, with 100 and 93.3?% of patients with BMI?<?35. In TOGa? group, 59?% of patients with an initial BMI?<?45 reached a BMI?<?35, in comparison to 48?% recorded in the whole group and to 14.3?% in patients with initial BMI????45.Conclusions
In selected patients, TOGa?, was associated with good results after two years in terms of weight loss, even in comparison with LRYGBP and BPD. Minimal trauma, absence of complications, and short hospital stay justify this procedure for patients with low BMI. 相似文献46.
47.
Milena Villarini Sara Levorato Tania Salvatori Elisabetta Ceretti Sara Bonetta Annalaura Carducci Tiziana Grassi Samuele Vannini Francesco Donato Silvia Bonetta Marco Verani Antonella de Donno Silvia Bonizzoni Alberto Bonetti Massimo Moretti Umberto Gelatti 《International journal of hygiene and environmental health》2018,221(6):883-892
Background
Recent data support the hypothesis that genetic damage occurring early in life during childhood can play an important role in the development of chronic diseases in adulthood, including cancer.Objectives
The objective of this paper, part of the MAPEC_LIFE project, is to describe the frequency of micronuclei and meta-nuclear alterations in exfoliated buccal cells of 6–8year-old Italian children recruited in five Italian towns (i.e., Brescia, Torino, Pisa, Perugia and Lecce) with different air pollution levels.Methods
About 200 children per town were recruited from primary schools. Biological samples were collected twice from the same children, in two different seasons (winter 2014-15 and late spring 2015). Cytogenetic damage was evaluated by the buccal micronucleus cytome assay.Results
Overall,n?=?1046 children represent the final cohort of the MAPEC_LIFE study. On the whole, the results showed a higher mean MN frequency in winter (0.42?±?0.54‰) than late-spring (0.22?±?0.34‰). MN frequency observed among the five Italian towns showed a trend that follows broadly the levels of air pollution in Italy: the highest MN frequency was observed in Brescia during both seasons, the lowest in Lecce (winter) and Perugia (late-spring).Conclusions
To the best of our knowledge, the number of recruited children included in the analysis (n?=?1046) is the highest compared to previous studies evaluating the frequency of MN in exfoliated buccal cells so far. MN frequency was associated with winter season and living in towns at various levels of air pollution, suggesting an important role of this exposure in determining early cytogenetic effects. 相似文献48.
49.
Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost
Vaidya JS Baum M Tobias JS Massarut S Wenz F Murphy O Hilaris B Houghton J Saunders C Corica T Roncadin M Kraus-Tiefenbacher U Melchaert F Keshtgar M Sainsbury R Douek M Harrison E Thompson A Joseph D 《International journal of radiation oncology, biology, physics》2006,66(5):1335-1338
PURPOSE: Patients undergoing breast-conserving surgery were offered boost radiotherapy with targeted intraoperative radiotherapy (TARGIT) using the Intrabeam system to test the feasibility, safety, and efficacy of the new approach. METHODS AND MATERIALS: We treated 302 cancers in 301 unselected patients. This was not a low-risk group. One-third of patients (98/301) were younger than 51 years of age. More than half of the tumors (172, 57%) were between 1 cm and 2 cm, and one-fifth (62, 21%) were >2 cm; 29% (86) had a Grade 3 tumor and, in 29% (87), axillary lymph nodes contained metastasis. After primary surgery, 20 Gy was delivered intraoperatively to the surface of the tumor bed, followed by external-beam radiotherapy (EBRT), but excluding the usual boost. RESULTS: The treatment was well tolerated. The follow-up ranged from 3 to 80 months (164 and 90 patients completed 2 and 3 years follow-up, respectively). Four patients (1.3%) had local recurrence. The Kaplan-Meier estimate of local recurrence is 2.6% (SE = 1.7) at 5 years. This compares favorably with the 4.3% recurrence rate in boosted patients from the EORTC boost study, in which only 8.1% patients were node-positive, as opposed to 29% in our series. CONCLUSION: Targeted intraoperative radiotherapy combined with EBRT results in a low local recurrence rate. This could be attributed to both accurate targeting and timeliness of the treatment. These data support the need for a randomized trial to test whether the TARGIT boost is superior to conventional external boost, especially in high-risk women. 相似文献
50.
Whole genome methylation profiles as independent markers of survival in stage iiic melanoma patients
L Sigalotti A Covre E Fratta G Parisi P Sonego F Colizzi S Coral S Massarut JM Kirkwood M Maio 《Journal of translational medicine》2012,10(1):185
ABSTRACT: BACKGROUND: The clinical course of cutaneous melanoma (CM) can differ significantly for patients with identical stages of disease, defined clinico-pathologically, and no molecular markers differentiate patients with such a diverse prognosis. This study aimed to define the prognostic value of whole genome DNA methylation profiles in stage III CM. METHODS: Genome-wide methylation profiles were evaluated by the Illumina Human Methylation 27 BeadChip assay in short-term neoplastic cell cultures from 45 stage IIIC CM patients. Unsupervised K-means partitioning clustering was exploited to sort patients into 2 groups based on their methylation profiles. Methylation patterns related to the discovered groups were determined using the nearest shrunken centroid classification algorithm. The impact of genome-wide methylation patterns on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analyses. RESULTS: Unsupervised K-means partitioning by whole genome methylation profiles identified classes with significantly different OS in stage IIIC CM patients. Patients with a "favorable" methylation profile had increased OS (P = 0.001, log-rank = 10.2) by Kaplan-Meier analysis. Median OS of stage IIIC patients with a "favorable" vs. "unfavorable" methylation profile were 31.5 and 10.4 months, respectively. The 5 year OS for stage IIIC patients with a "favorable" methylation profile was 41.2% as compared to 0% for patients with an "unfavorable" methylation profile. Among the variables examined by multivariate Cox regression analysis, classification defined by methylation profile was the only predictor of OS (Hazard Ratio = 2.41, for "unfavorable" methylation profile; 95% Confidence Interval: 1.02-5.70; P = 0.045). A 17 gene methylation signature able to correctly assign prognosis (overall error rate = 0) in stage IIIC patients on the basis of distinct methylation-defined groups was also identified. CONCLUSIONS: A discrete whole-genome methylation signature has been identified as molecular marker of prognosis for stage IIIC CM patients. Its use in daily practice is foreseeable, and promises to refine the comprehensive clinical management of stage III CM patients. 相似文献