全文获取类型
收费全文 | 101篇 |
免费 | 3篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 3篇 |
基础医学 | 41篇 |
内科学 | 7篇 |
皮肤病学 | 2篇 |
神经病学 | 22篇 |
特种医学 | 2篇 |
外科学 | 2篇 |
综合类 | 3篇 |
预防医学 | 4篇 |
眼科学 | 1篇 |
肿瘤学 | 15篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 2篇 |
2020年 | 8篇 |
2019年 | 6篇 |
2018年 | 2篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 2篇 |
2013年 | 2篇 |
2012年 | 4篇 |
2011年 | 5篇 |
2010年 | 1篇 |
2009年 | 5篇 |
2008年 | 9篇 |
2007年 | 12篇 |
2006年 | 8篇 |
2005年 | 7篇 |
2004年 | 3篇 |
2003年 | 3篇 |
2002年 | 1篇 |
2001年 | 5篇 |
1998年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有104条查询结果,搜索用时 15 毫秒
1.
《Revista espa?ola de cardiología》2022,75(3):242-250
Introduction and objectivesTPM1 is one of the main hypertrophic cardiomyopathy (HCM) genes. Clinical information on carriers is relatively scarce, limiting the interpretation of genetic findings in individual patients. Our aim was to establish genotype-phenotype correlations of the TPM1 p.Arg21Leu variant in a serie of pedigrees.MethodsTPM1 was evaluated by next-generation sequencing in 10 561 unrelated probands with inherited heart diseases. Familial genetic screening was performed by the Sanger method. We analyzed TPM1 p.Arg21Leu pedigrees for cosegregation, clinical characteristics, and outcomes. We also estimated the geographical distribution of the carrier families in Portugal and Spain.ResultsThe TPM1 p.Arg21Leu variant was identified in 25/4099 (0.61%) HCM-cases, and was absent in 6462 control individuals with other inherited cardiac phenotypes (P < .0001). In total, 83 carriers (31 probands) were identified. The combined LOD score for familial cosegregation was 3.95. The cumulative probability of diagnosis in carriers was 50% at the age of 50 years for males, and was 25% in female carriers. At the age of 70 years, 17% of males and 46% of female carriers were unaffected. Mean maximal left ventricular wall thickness was 21.4 ± 7.65 mm. Calculated HCM sudden death risk was low in 34 carriers (77.5%), intermediated in 8 (18%), and high in only 2 (4.5%). Survival free of cardiovascular death or heart transplant was 87.5% at 50 years. Six percent of carriers were homozygous and 18% had an additional variant. Family origin was concentrated in Galicia, Extremadura, and northern Portugal, suggesting a founder effect.ConclusionsTPM1 p.Arg21Leu is a pathogenic HCM variant associated with late-onset/incomplete penetrance and a generally favorable prognosis. 相似文献
2.
《International journal of pediatric otorhinolaryngology》2014,78(11):1828-1832
ObjectiveMutations in the SLC26A4 gene cause both Pendred syndrome and autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNB4 locus. The SLC26A4 mutations vary among different communities. Previous studies have shown that mutations in the SLC26A4 gene are responsible for the more common syndromic hereditary hearing loss in Iran. This study assesses the possibility of a founder mutation for Pendred syndrome in northwest Iran.Materials and methodsIn this study, we performed comprehensive clinical and genetic evaluations in two unrelated families from northwest Iran with nine members affected by hearing loss (HL). After testing short tandem repeat (STR) markers to confirm linkage to the SLC26A4 locus, we screened the SLC26A4 gene by Sanger sequencing of all 21 exons, exon–intron boundaries and the promoter region for any causative mutation. We identified the same causative mutation in these two families as we had detected earlier in two other Azeri families from northwest Iran. To investigate the possibility of a founder effect in these four families, we conducted haplotype analysis, and 14 single nucleotide polymorphisms (SNPs) throughout the SLC26A4 gene were genotyped.ResultsPatients in the two families showed the phenotype of Pendred syndrome. A known frameshift mutation (c.965insA, p.N322Fs7X) in exon 8 was identified in the two families, which was the same mutation that we detected previously in two other Azeri families. The results of haplotype analysis showed that all 15 patients from four families shared the founder mutation. Common haplotypes were not observed in noncarrier members.ConclusionsBased on the results of our two studies, the c.965insA mutation has only been described in Iranian families from northwest Iran, so there is evidence for a founder mutation originating in this part of Iran. 相似文献
3.
4.
Hainan Island is the southernmost and smallest Chinese province, isolated from the mainland. The Li and Han ethnic groups account for over 98% of the population on the island. However, the Li ethnic group is an indigenous community of Hainan Island, with great differences in culture, language and origin with respect to the Han, the largest ethnic group. Here, we studied these two ethnic groups from the perspective of the Y-chromosome single nucleotide polymorphisms (Y-SNPs) and short tandem repeats (Y-STRs) to unravel their forensic and phylogenetic characteristics. A total of 302 unrelated male samples from the Li and Han ethnic groups in Hainan Island were genotyped by a combination of three separate typing systems (next-generation sequencing and pyrosequencing for the Y-SNPs and capillary electrophoresis for the Y-STRs), a previously developed high-resolution panel containing 141 Y-SNPs and 27 Y-STRs. The haplotype diversity of the Li ethnic group reached 0.9997, and 49 terminal haplogroups were observed in the Li and Han ethnic groups. Haplogroup O1b1a1a1a1a1b-CTS5854 was the most predominant haplogroup, including 44.12% of Li individuals. Median-joining trees showed little gene flow between the Li and Han individuals, as well as between the Li and other ethnic groups in Hainan Island. Our results indicated that 1) in contrast with the Han ethnic group, a low degree of genetic diversity was observed in the Li ethnic group; 2) there was limited gene flow between the Li and Han ethnic groups; and 3) founder effect was identified in the Li ethnic group in Hainan Island. 相似文献
5.
《Nefrología : publicación oficial de la Sociedad Espa?ola Nefrologia》2020,40(5):536-542
ObjectiveTo demonstrate that the variant not described in PKD1 gene c.7292T> A, identified in four families from the Alpujarra in Granada, is the cause of autosomal dominant polycystic kidney disease (ADPKD). This variant consists of a transversion of thymine (T) by adenine (A) that at the level of the Polycystin 1 protein produces a change of leucine (Leu / L) by Glutamine (Gln / Q) in position 2431 (p.Leu2431Gln).MethodSociodemographic and clinical variables were registered using clinical histories, genealogical trees, ultrasounds and genetic analysis to ADPKD and healthy individuals belonging to these families in the context of segregation study.ResultsAll PKD individuals carried the c.7292T>A variant in heterozygosis, whereas healthy ones did not. Among all ADPKD patients, 62.9% were women. ADPKD diagnosis was made at 29.3 ± 15.82 years, after having the first child in 64.8%. The main reasons for diagnosis were family history and hematuria episodes. The onset of renal replacement therapy (RRT) occurred at 55.8 ± 7.62 years (range 44-67), and death at 63 ± 92.2 years (range 48-76), being the cause unknown, cardiovascular and insufficiency kidney the most frequent; the median of renal survival was established at 58.5 ± 0.77 years and the median survival of patients at 67.2 ± 3.54 years. No differences in kidney and patient survivals were observed according to sex. Among deceased patients, 52.2% required RRT and 94.4% suffered from renal failure.ConclusionsThe variant c.7292T>A in PKD1 gene is responsible for the disease, and its distribution in the Alpujarra region of Granada suggests a founder effect. In ADPKD it is necessary to perform segregation studies that help us to reclassify genetic variants, in this case from indeterminate to pathogenic. 相似文献
6.
《European journal of medical genetics》2020,63(3):103753
Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome (LS), is a common cancer-predisposing syndrome. This study aimed to investigate the spectrum of germ-line mutations in Russian LS patients. LS-related mismatch repair (MMR) genes were analyzed in 16 patients, who were forwarded to genetic testing due to strong clinical features of LS and had high-level microsatellite instability (MSI-H) in the tumor (n = 14) or unknown MSI status (n = 2). In addition, 672 consecutive colorectal cancer (CRC) cases were screened for family history; 15 patients were younger than 50 years and reported 2 or more instances of LS-related cancers in 1st- or 2nd-degree relatives. Seven of these cases demonstrated MSI-H and therefore were subjected to DNA germ-line testing. Overall, 17/23 (74%) subjects carried LS-associated gene variants (MLH1: 10; MSH2: 4; MSH6: 2; PMS2: 1), with 2 alleles (MLH1 c.677G > T and MSH2 с.1906G > C) detected twice. Testing for recurrent mutations of 30 consecutive MSI-H CRCs led to the identification of 2 additional subjects with LS. The analysis of all relevant publications identified 28 unrelated LS patients presented in Russian medical literature and 3 unrelated Russian LS subjects described in international journals. Overall, 15/49 (31%) genetic defects revealed in Russian LS patients were represented by six recurrent alleles (MLH1: c.350C > T, c.677G > T, c.1852_1854del; MSH2: c.942+3A > T, c.1861C > T, с.1906G > C). We conclude that the founder effect for LS in Russia is seemingly less pronounced than the one for hereditary breast-ovarian cancer syndrome, however testing for recurrent LS mutations may be considered feasible in some circumstances. 相似文献
7.
Population genetics of phenylketonuria 总被引:1,自引:0,他引:1
Phenylketonuria (PKU) is an autosomal recessive disorder caused by a large number of mutations at the phenylalanine hydroxylase (PAH) locus, most of which are strongly associated with specific RFLP or VNTR haplotypes. One of the major questions remaining in PKU research is why this apparently maladaptive disorder has been maintained at a frequency of approximately 1 in 10000 among Caucasians. A growing number of studies have provided evidence that both the relatively high frequency of PKU and the strong mutation/haplotype associations might reflect the existence of multiple founding populations for PKU. Examples of putative founding populations for PKU in both Europe and Asia will be presented. Some PAH mutations are associated with multiple haplotypes, suggesting recurrence. Evidence for and against recurrence as the mechanism responsible for the association of the R408W mutation with RFLP haplotypes 1 and 2 will be discussed. 相似文献
8.
Rump P Lemmink HH Verschuuren-Bemelmans CC Grootscholten PM Fock JM Hayflick SJ Westaway SK Vos YJ van Essen AJ 《Neurogenetics》2005,6(4):201-207
Mutation analysis was performed in four apparently unrelated Dutch families with pantothenate kinase-associated neurodegeneration,
formerly known as Hallervorden-Spatz syndrome. A novel 3-bp deletion encompassing the nucleotides GAG at positions 1,142 to
1,144 of exon 5 of the PANK2 gene was found in all patients. One patient was compound heterozygous; she also carried a novel nonsense mutation (Ser68Stop).
The other patients were homozygous for the 1142_1144delGAG mutation. The 1142_1144delGAG mutation was also found in a German
patient of unknown descent. We used polymorphic microsatellite markers flanking the PANK2 gene (spanning a region of approximately 8 cM) for haplotype analyses in all these families. A conserved haplotype of 1.5 cM
was found for the 1142_1144delGAG mutation carriers. All the Dutch families originated from the same geographical region within
the Netherlands. The results indicate a founder effect and suggest that the 1142_1144delGAG mutation probably originated from
one common ancestor. It was estimated that this mutation arose at the beginning of the ninth century, approximately 38 generations
ago. 相似文献
9.
The incidence of Tay-Sachs disease (TSD) carriers, as defined by enzyme assay, is 1:29 among Ashkenazi Jews and 1:110 among Moroccan Jews. An elevated carrier frequency of 1:140 was also observed in the Iraqi Jews (IJ), while in other Israeli populations the worlds pan-ethnic frequency of approximately 1:280 has been found. Recently a novel mutation, G749T, has been reported in 38.7% of the IJ carriers (24/62). Here we report a second novel HEXA mutation specific to the IJ TDS carriers: a substitution of cytosine 1351 by guanosine (C1351G), resulting in the change of leucine to valine in position 451. This mutation was found in 33.9% (21/62) of the carriers and in none of 100 non-carrier IJ. In addition to the two specific mutations, 14.5% (9/62) of the IJ carriers bear a known Jewish mutation (Ashkenazi or Moroccan) and 11.3% (7/62) carry a known non-Jewish mutation. In 1 DNA sample no mutation has yet been detected. To investigate the genetic history of the IJ-specific mutations (C1351G and G749T), the allelic distribution of four polymorphic markers (D15S131, D15S1025, D15S981, D15S1050) was analyzed in IJ heterozygotes and ethnically matched controls. Based on linkage disequilibrium, recombination factor () between the markers and mutated loci, and the population growth correction, we deduced that G749T occurred in a founder ancestor 44.8±14.2 generations (g) ago [95% confidence interval (CI) 17.0–72.6 g] and C1351G arose 80.4±35.9 g ago (95% CI 44.5–116.3 g). Thus, the estimated dates for introduction of mutations are: 626±426 A.D. (200–1052 A.D.) for G749T and 442±1077 B.C. (1519 B.C. to 635 A.D.) for C1351G. 相似文献
10.
Elsebet Ostergaard Frodi Joensen Karin Sundberg Morten Duno Flemming J Hansen Mustafa Batbayli Nicolina Sørensen Alfred Peter Born 《Acta paediatrica (Oslo, Norway : 1992)》2012,101(11):e509-e513
Aim: The aim of the study was to identify the genetic background for Aicardi–Goutieres syndrome (AGS) in the Faroe Islands. Methods: Four patients with AGS were identified. The patients had a variable phenotype, from a severe prenatal form with intrauterine foetal death to a milder phenotype, albeit still with an early onset, within the first 2–3 months. Results: A genome‐wide search for homozygosity revealed one single 15.6 Mb region of homozygosity on chromosome 13, which included RNASEH2B, where a splice site mutation c.322‐3C>G was identified. Screening of 170 anonymous Faroese controls revealed a carrier frequency of approximately 1.8%, corresponding to an incidence of AGS in the Faroe Islands of around 1 in 12 300. Conclusion: The previously identified RNASEH2B mutations comprise altogether 20 mutations (missense, nonsense and splice site) with all patients harbouring at least one missense mutation. The severe phenotype of the Faroese patients compared with the previously reported patients with RNASEH2B mutations may be caused by the presence of two null alleles (although some residual normal splicing cannot be ruled out), whereas patients with one or two missense mutations may have some, albeit abnormal, RNASEH2B proteins, and hence some residual activity of RNASEH2B, explaining their milder phenotype. 相似文献