全文获取类型
收费全文 | 324篇 |
免费 | 22篇 |
专业分类
儿科学 | 8篇 |
妇产科学 | 3篇 |
基础医学 | 94篇 |
口腔科学 | 1篇 |
临床医学 | 31篇 |
内科学 | 94篇 |
皮肤病学 | 2篇 |
神经病学 | 17篇 |
特种医学 | 18篇 |
外科学 | 21篇 |
综合类 | 1篇 |
预防医学 | 15篇 |
药学 | 7篇 |
肿瘤学 | 34篇 |
出版年
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 7篇 |
2013年 | 12篇 |
2012年 | 25篇 |
2011年 | 23篇 |
2010年 | 15篇 |
2009年 | 21篇 |
2008年 | 22篇 |
2007年 | 20篇 |
2006年 | 13篇 |
2005年 | 22篇 |
2004年 | 19篇 |
2003年 | 16篇 |
2002年 | 17篇 |
2001年 | 16篇 |
2000年 | 22篇 |
1999年 | 12篇 |
1998年 | 4篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有346条查询结果,搜索用时 15 毫秒
1.
Raj P. Kapur Ian Neilson Robert M.W. Hofstra Lynda W. Holloway Ron C. Michaelis Kathleen A. Leppig 《American journal of medical genetics. Part A》2002,108(1):51-56
Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM‐mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease–associated gene to cause intestinal aganglionosis. © 2002 Wiley‐Liss, Inc. 相似文献
2.
The Annexin code: revealing endocarditis 总被引:1,自引:0,他引:1
A 54-year-old woman presented to our hospital after an episodeof fever of unknown origin. The fever had occurred 6 weeks priorto presentation and had subsided spontaneously. The patienthad no relevant prior medical 相似文献
3.
Heart failure is the number one reason for hospital admissionin patients above 65 years of age. It is predicted that thenumber of heart failure patients will almost double in the next20 years. Ischaemic and hypertensive heart disease are the majorcauses of this disabling disease. Approximately 22% of womenand 46% of men who have had a myocardial infarction will developheart failure within 6 years.1 Still, hypertension is a chiefcause of cardiac failure: diastolic dysfunction accounts for>50% of all heart failure patients.2 In the world we livein, an increasing number of people become at risk of developinghypertension heart 相似文献
4.
Burzynski GM Nolte IM Osinga J Ceccherini I Twigt B Maas S Brooks A Verheij J Plaza Menacho I Buys CH Hofstra RM 《European journal of human genetics : EJHG》2004,12(8):604-612
Hirschsprung disease (HSCR), a congenital disorder characterized by intestinal obstruction due to absence of enteric ganglia along variable lengths of the intestinal tract, occurs both in familial and sporadic cases. RET mutations have been found in approximately 50% of the families, but explains only a minority of sporadic cases. This study aims at investigating a possible role of RET in sporadic HSCR patients. Haplotypes of 13 DNA markers, within and flanking RET, have been determined for 117 sporadic HSCR patients and their parents. Strong association was observed for six markers in the 5' region of RET. The largest distortions in allele transmission were found at the same markers. One single haplotype composed of these six markers was present in 55.6% of patients versus 16.2% of controls. Odds ratios (ORs) revealed a highly increased risk of homozygotes for this haplotype to develop HSCR (OR>20). These results allowed us to conclude that RET plays a crucial role in HSCR even when no RET mutations are found. An unknown functional disease variant(s) with a dosage-dependent effect in HSCR is likely located between the promoter region and exon 2 of RET. 相似文献
5.
6.
Hofstra RM Mulder IM Vossen R de Koning-Gans PA Kraak M Ginjaar IB van der Hout AH Bakker E Buys CH van Ommen GJ van Essen AJ den Dunnen JT 《Human mutation》2004,23(1):57-66
Duchenne and Becker muscular dystrophy (DMD and BMD) are caused by mutations in the dystrophin gene. Large rearrangements in the gene are found in about two-thirds of DMD patients, with approximately 60% carrying deletions and 5-10% carrying duplications. Most of the remaining 30-35% of patients are expected to have small nucleotide substitutions, insertions, or deletions. To detect these subtle changes within the coding and splice site determining sequences of the dystrophin gene, we established a semiautomated denaturing gradient gel electrophoresis (DGGE) mutation scanning system. The DGGE scan covers the dystrophin gene with 95 amplicons, PCRed either individually or in a multiplex setup. PCR and pooling were performed semiautomatically, using a pipetting robot and 384-well plates, enabling concurrent amplification of DNA of four patients in one run. Amplification of individual fragments was performed using one PCR program. The products were pooled just before gel loading; DGGE requires only a single gel condition. Validation was performed using DNA samples harboring 39 known DMD variants, all of which could be readily detected. DGGE mutation scanning was applied to analyze 135 DMD/BMD patients and potential DMD carriers without large deletions or duplications. In DNA from 25 out of 44 DMD patients (57%) and from 5 out of 39 BMD patients (13%), we identified clear pathogenic changes. All mutations were different, with the exception of one DMD mutation, which occurred twice. In DNA from 10 out of 44 potential DMD carriers, including four obligate carriers, we detected causative changes, including one pathogenic change in every obligate carrier. In addition to these pathogenic changes, we detected 15 unique unclassified variants, i.e., changes for which a pathogenic nature is uncertain. 相似文献
7.
8.
T Kahraman J W B de Groot C Rouwe R M W Hofstra Th P Links R H Sijmons J Th M Plukker 《European journal of surgical oncology》2003,29(4):331-335
AIMS: Germline mutated RET proto-oncogene, causing multiple endocrine neoplasia (MEN)-2a syndrome is the indication for prophylactic total thyroidectomy. Literature regarding the risk and the extent of early surgical intervention is scarce and the optimum age for surgery is still controversial. To optimize management in these young children we evaluate our experience and results. PATIENTS AND METHODS: From 1990 to 2001 preventive total thyroidectomy was performed in 13 MEN-2a gene carriers (4 boys and 9 girls; median age 7 (4-14) years). Preoperative assessment, surgical procedure, pathological examination, postoperative complications and treatment results were studied. RESULTS:Surgery existed of a total thyroidectomy alone (n=3) in children with normal basal calcitonin and in combination with tracheo-esophageal exploration (n=6) or central compartment dissection (n=4) in case of abnormal calcitonin levels. Eight children presented with medullary thyroid cancer (MTC), three (median: 5 (4-12) years) with microscopic MTC and five (median 6 (4-14) years) with frank invasive MTC. Four of these five patients were younger than 6 years. Except for long-lasting hypoparathyroidism in one patient there were no complications. At a median follow-up of 6.5 years all patients are disease free. CONCLUSION: MTC in RET mutated MEN-2a gene carriers in childhood are found at the age of 4 years. Therefore, DNA testing should be done preferably before that age. Preventive surgery can be performed safely at that age and may be limited to total thyroidectomy when baseline calcitonin levels are normal. 相似文献
9.
Jesse Limaheluw Gertjan Medema Nynke Hofstra 《International journal of hygiene and environmental health》2019,222(5):856-863
The protozoan pathogen Cryptosporidium is an important cause of diarrhoeal disease, but in many contexts its burden remains uncertain. The Global Waterborne Pathogen model for Cryptosporidium (GloWPa-Crypto) predicts oocyst concentrations in surface water at 0.5 by 0.5° (longitude by latitude) resolution, allowing us to assess the burden specifically associated with the consumption of contaminated surface water at a large scale. In this study, data produced by the GloWPa-Crypto model were used in a quantitative microbial risk assessment (QMRA) for sub-Saharan Africa, one of the regions most severely affected by diarrhoeal disease. We first estimated the number of people consuming surface water in this region and assessed both direct consumption and consumption from a piped (treated) supply. The disease burden was expressed in disability adjusted life years (DALYs). We estimate an annual number of 4.3 × 107 (95% uncertainty interval [UI] 7.4 × 106–5.4 × 107) cases which represent 1.6 × 106 (95% UI 3.2 × 105–2.3 × 106) DALYs. Relative disease burden (DALYs per 100,000 persons) varies widely, ranging between 1.3 (95% UI 0.1–5.7) for Senegal and 1.0 × 103 (95% UI 4.2 × 102–1.4 × 103) for Eswatini. Countries that carry the highest relative disease burden are primarily located in south and south-east sub-Saharan Africa and are characterised by a relatively high HIV/AIDS prevalence. Direct surface water consumption accounts for the vast majority of cases, but the results also point towards the importance of stable drinking water treatment performance. This is, to our knowledge, the first study to utilise modelled data on pathogen concentrations in a large scale QMRA. It demonstrates the potential value of such data in epidemiological research, particularly regarding disease aetiology. 相似文献
10.