全文获取类型
收费全文 | 319篇 |
免费 | 22篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 3篇 |
妇产科学 | 2篇 |
基础医学 | 69篇 |
口腔科学 | 3篇 |
临床医学 | 27篇 |
内科学 | 44篇 |
皮肤病学 | 5篇 |
神经病学 | 19篇 |
特种医学 | 70篇 |
外科学 | 31篇 |
综合类 | 1篇 |
预防医学 | 6篇 |
眼科学 | 18篇 |
药学 | 9篇 |
肿瘤学 | 35篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 7篇 |
2020年 | 4篇 |
2019年 | 11篇 |
2018年 | 4篇 |
2017年 | 14篇 |
2016年 | 6篇 |
2015年 | 13篇 |
2014年 | 9篇 |
2013年 | 10篇 |
2012年 | 45篇 |
2011年 | 24篇 |
2010年 | 13篇 |
2009年 | 12篇 |
2008年 | 23篇 |
2007年 | 16篇 |
2006年 | 17篇 |
2005年 | 8篇 |
2004年 | 7篇 |
2003年 | 17篇 |
2002年 | 9篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1987年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1978年 | 2篇 |
排序方式: 共有343条查询结果,搜索用时 15 毫秒
81.
Antonio Brage Santiago Tomé Aranzazu García Ángel Carracedo Antonio Salas 《Hepatology research》2007,37(1):18-26
Wilson disease (WD) results when specific mutations occur at the ATP7B gene. The presence of mutations in the ATP7B gene was studied in the coding region and the intron-exon boundaries in 15 WD Spanish patients, and their first-degree relatives when possible. A total of 20 nucleotide sequence changes were detected, 18 missense and two splicing mutations. Six of these variants were classified as disease-causing mutations, five missense, and one splicing; four of them have been previously described (M645R, A1065P, H1069Q, and 3060 + 5G > T), whereas two were novel (P768L and A990P). No mutation was clearly prevalent, although the H1069Q mutation predominated, nor did a good phenotype-genotype correlation exist. The two new mutations described were manifested as an asymptomatic increase in serum transaminases. The remaining 14 changes were classified as polymorphisms and their potential effects on protein function are discussed. The identification of mutations in the ATP7B gene has allowed a conclusive diagnosis to be made of WD in patients presenting neurological phenotype or neurological of hepatic phenotype, who would otherwise not have been diagnosed using classical criteria. WD patients could start chelating treatment earlier on and possibly modify the natural progression of the disease. 相似文献
82.
83.
A maternally inherited 16p13.11‐p12.3 duplication concomitant with a de novo SOX5 deletion in a male patient with global developmental delay,disruptive and obsessive behaviors and minor dysmorphic features
下载免费PDF全文
![点击此处可从《American journal of medical genetics. Part A》网站下载免费的PDF全文](/ch/ext_images/free.gif)
84.
Dalemari Crowther‐Swanepoel Mahmoud Mansouri Anna Enjuanes Ana Vega Karin E. Smedby Clara Ruiz‐Ponte Jesper Jurlander Gunnar Juliusson Emilio Montserrat Daniel Catovsky Elias Campo Angel Carracedo Richard Rosenquist Richard S. Houlston 《British journal of haematology》2010,150(4):473-479
A recent genome wide association study of chronic lymphocytic leukaemia (CLL) provided evidence that common variation at 2q13 (rs17483466), 2q37.1 (rs13397985), 6p25.3 (rs872071), 11q24.1 (rs735665), 15q23 (rs7176508) and 19q13.32 (rs11083846) affects CLL risk. To verify and further explore the relationship between these variants and CLL risk we genotyped case‐control datasets from Spain and Sweden (824 cases, 850 controls). Combined data provided statistically significant support for an association between genotypes at rs13397985, rs872071, rs735665, rs7176508 and rs11083846 and CLL risk. CLL risk increased with increasing numbers of risk alleles (Ptrend = 1·40 × 10?15), consistent with a polygenic model of disease susceptibility. These data validate the relationship between common variation and risk of CLL. 相似文献
85.
Fernández-Marmiesse A Salas A Vega A Fernández-Lorenzo JR Barreiro J Carracedo A 《Human mutation》2006,27(2):214
Hyperinsulinism of Infancy (HI) is a clinical disorder characterized by deregulation of insulin secretion that leads to profound hypoglycemia. Mutations in genes encoding the ATP-regulated potassium channels of the pancreatic beta-cell, namely ABCC8 (SUR1) and KCNJ11 (Kir6.2), are the major genetic known cause of the disease. To elucidate the genetic etiology of HI in the uncharacterized Spanish population, we conducted extensive sequencing analysis of the ABCC8 (83.5Kb) and KCNJ11 (1.7Kb) genes in 34 Spanish HI patients. Mutations in ABCC8 were detected for both alleles in 13 patients, while ten patients carried only one mutation in one of the ABCC8 alleles. We have detected 22 novel and seven previously described mutations in ABCC8, approximately 60% of them lead to a premature termination signal, which would result in truncated SUR1 proteins. No mutations were found in the KCNJ11 gene. In addition, we report for the first time a 3914bp macrodeletion associated with the HI disorder. The potential pathogenicity of several additional variants is discussed. The spatial pattern of three pathological mutations suggests possible geographical founder effects. This work reveals for first time the involvement of KATP channels in the pathogenesis of an important proportion (approximately 68%) of Spanish HI patients. The spectrum of mutations in Spanish HI patients provides an important tool for diagnosis and prognosis of HI patients in the Spanish population, as well as for genetic counseling of HI families. 相似文献
86.
Ruiz-Ponte C Carracedo A Barros F 《Clinica chimica acta; international journal of clinical chemistry》2006,363(1-2):138-146
BACKGROUND: Gene dosage determination is an increasingly important field for the study of genome variation and organization. In parallel, the advances in our understanding of the genetic basis of disease have produced an exponential increase in the demand for molecular diagnostic analyses. Although efforts have been spent on increasing both the accuracy and the throughput of the gene dosage analysis, the success has been limited. METHODS: A large number of suitable methods has been proposed; most are based on quantitative real-time PCR or amplification of multiple targets. A new approach exploits the differences between fluorescent signals of SNP alleles in heterozygous samples to assess duplications. The SNP typing-dependent fluorescent signal allelic asymmetry is an intrinsic characteristic of a SNP typing assay and can lead to a simple and cost-effective gene dosage method. This strategy provides sufficient throughput and sensitivity for duplication analysis. CONCLUSIONS: There are advantages and disadvantages of real-time methodology when applying the approach to the molecular diagnostic field. 相似文献
87.
Genomic rearrangements at the BRCA1 locus in Spanish families with breast/ovarian cancer 总被引:6,自引:0,他引:6
de la Hoya M Gutiérrez-Enríquez S Velasco E Osorio A Sanchez de Abajo A Vega A Salazar R Esteban E Llort G Gonzalez-Sarmiento R Carracedo A Benítez J Miner C Díez O Díaz-Rubio E Caldes T 《Clinical chemistry》2006,52(8):1480-1485
BACKGROUND: Large genomic rearrangements (LGRs) account for a substantial proportion of the BRCA1 disease-causing changes, or variations, identified in families with hereditary breast/ovarian cancer [HB(O)C]. Great differences in the spectrum and prevalence of BRCA1 LGR have been observed among populations. Here we report the first comprehensive analysis of BRCA1 LGRs conducted in Spain. METHODS: We used multiplex ligation-dependent probe amplification (MLPA) to screen for BRCA1 LGRs in the index case individuals of 384 HB(O)C families who previously tested negative for BRCA1 and BRCA2 point variations, small insertions, and deletions. An alternative set of MLPA probes, long-range PCR, and real-time PCR were used to confirm positive results. RESULTS: We have identified 8 different BRCA1 rearrangements (del exon 1-24, del exon 8-13, del exon 11-15, del exon 14, dup exon 19-20, dup exon 20, exon 21-22 amplification, and del exon 23-24). With the exception of del exon 8-13, they are novel alterations. Overall, BRCA1 LGRs explain 1.4% of the Spanish HB(O)C families, and they account for 8.2% of all BRCA1 pathogenic variations identified in our study population. BRCA1 genetic variants affecting hybridization of commercially available MLPA probes are very rare in our population. CONCLUSIONS: Screening for BRCA1 LGRs should be mandatory in Spanish HB(O)C families. A high proportion of country-specific rearrangements are scattered along the gene. MLPA is a robust method to screen for LGRs in our population. MLPA analysis of positive samples with an alternative set of probes, together with long-range PCR and real-time PCR, is a feasible approach to confirm results in cases in which LGR breakpoints have not been characterized. 相似文献
88.
89.
90.
We determined serum transferrin receptor (sTfR), serum erythropoietin and hematologic and biochemical iron parameters in 251 healthy children. The levels of sTfR were significantly higher in children with storage iron deficiency but had a poor sensivity for recognizing iron deficiency without anemia. When ferritin values cannot accurately demonstrate the iron deficiency in children, the sTfR/ferritin ratio or sTfR-log ferritin is recommended to discriminate iron deficiency in the absence of anemia. 相似文献