全文获取类型
收费全文 | 122篇 |
免费 | 12篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 5篇 |
妇产科学 | 4篇 |
基础医学 | 14篇 |
口腔科学 | 1篇 |
临床医学 | 9篇 |
内科学 | 40篇 |
神经病学 | 18篇 |
特种医学 | 1篇 |
外科学 | 4篇 |
综合类 | 4篇 |
预防医学 | 7篇 |
眼科学 | 2篇 |
药学 | 19篇 |
中国医学 | 2篇 |
肿瘤学 | 3篇 |
出版年
2022年 | 6篇 |
2021年 | 9篇 |
2020年 | 8篇 |
2019年 | 3篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 5篇 |
2014年 | 3篇 |
2013年 | 17篇 |
2012年 | 22篇 |
2011年 | 13篇 |
2010年 | 5篇 |
2008年 | 9篇 |
2007年 | 5篇 |
2006年 | 2篇 |
2005年 | 3篇 |
2004年 | 1篇 |
2003年 | 2篇 |
2002年 | 1篇 |
1999年 | 1篇 |
1997年 | 1篇 |
1993年 | 1篇 |
排序方式: 共有135条查询结果,搜索用时 15 毫秒
1.
Sanna Matilainen Pirjo Isohanni Liliya Euro Tuula L?nnqvist Helena Pihko Tero Kivel? Sakari Knuutila Anu Suomalainen 《European journal of human genetics : EJHG》2015,23(3):325-330
Mutations in SUCLA2, encoding the ß-subunit of succinyl-CoA synthetase of Krebs cycle, are one cause of mitochondrial DNA depletion syndrome. Patients have been reported to have severe progressive childhood-onset encephalomyopathy, and methylmalonic aciduria, often leading to death in childhood. We studied two families, with children manifesting with slowly progressive mitochondrial encephalomyopathy, hearing impairment and transient methylmalonic aciduria, without mtDNA depletion. The other family also showed dominant inheritance of bilateral retinoblastoma, which coexisted with mitochondrial encephalomyopathy in one patient. We found a variant in SUCLA2 leading to Asp333Gly change, homozygous in one patient and compound heterozygous in one. The latter patient also carried a deletion of 13q14 of the other allele, discovered with molecular karyotyping. The deletion spanned both SUCLA2 and RB1 gene regions, leading to manifestation of both mitochondrial disease and retinoblastoma. We made a homology model for human succinyl-CoA synthetase and used it for structure–function analysis of all reported pathogenic mutations in SUCLA2. On the basis of our model, all previously described mutations were predicted to result in decreased amounts of incorrectly assembled protein or disruption of ADP phosphorylation, explaining the severe early lethal manifestations. However, the Asp333Gly change was predicted to reduce the activity of the otherwise functional enzyme. On the basis of our findings, SUCLA2 mutations should be analyzed in patients with slowly progressive encephalomyopathy, even in the absence of methylmalonic aciduria or mitochondrial DNA depletion. In addition, an encephalomyopathy in a patient with retinoblastoma suggests mutations affecting SUCLA2.Mitochondrial diseases are caused by genetic defects in nuclear or mitochondrial DNA (mtDNA) that disrupt function of the respiratory chain, compromising the synthesis of ATP. Most childhood-onset phenotypes are caused by autosomal recessive mutations in nuclear-encoded mitochondrial proteins. Mitochondrial diseases can manifest at any age, with almost any symptom, in almost any tissue, although the tissues with the largest dependence on oxidative energy supply, such as the central nervous system, sensory organs and skeletal muscle,1 are most commonly affected. The wide clinical and genetic heterogeneity with overlapping phenotypes makes the diagnostics of mitochondrial diseases challenging.2mtDNA depletion syndrome is associated with many clinical phenotypes and has a variable genetic background. It can be caused by several nuclear genes, which typically impair mtDNA replication, repair or nucleotide synthesis.3 One of these genes is SUCLA2, encoding the β-subunit of the Krebs cycle enzyme ADP-forming succinyl-CoA synthetase (SCS-A). SCS catalyzes the reversible conversion of succinyl-CoA to succinate, accompanied by substrate-level phosphorylation of ADP or GDP.4 The enzyme is a heterodimer composed of a catalytic α-subunit, encoded by SUCLG1 and a β-subunit that determines the enzymes'' substrate specificity for either ADP (SUCLA2) or GDP (SUCLG2). SCS is widely expressed in mammalian tissues, with predominance of either the ADP- or GDP-forming form in each tissue. SUCLG1 is ubiquitously expressed, whereas expression of SUCLA2 dominates in catabolic tissues, in which the main source of energy is ATP, such as the brain, and is induced in heart and skeletal muscle.4, 5 Patients with SUCLA2 mutations typically have progressive childhood-onset Leigh-like encephalomyopathy associated with dystonia, hypotonia, sensorineural hearing deficit, lesions of the basal ganglia, depletion of mtDNA and methylmalonic aciduria.3, 6 Over 20 patients and five different mutations in SUCLA2 have been described.6, 7, 8, 9, 10We report here molecular basis of mitochondrial encephalomyopathy, also combined with bilateral retinoblastoma, in patients with clinical symptoms or signs previously described in association with SUCLA2 mutations: encephalomyopathy with hearing deficit and methylmalonic aciduria. 相似文献
2.
3.
Tamayev Liliya Schreiber Letizia Marciano Adi Bar Jacob Kovo Michal 《Archives of gynecology and obstetrics》2020,301(5):1147-1151
Archives of Gynecology and Obstetrics - Adaptations to pathological intrauterine environment might differ in relation to fetal gender. We aimed to study sex-specific differences in placental... 相似文献
4.
Luo F Leckman JF Katsovich L Findley D Grantz H Tucker DM Lombroso PJ King RA Bessen DE 《Pediatrics》2004,113(6):e578-e585
5.
Daniel F. Gluzman Iryna V. Abramenko Liliya M. Sklyarenko Valentina A. Nadgornaya Michael P. Zavelevich Nadia I. Bilous Ludmila Yu Poludnenko 《Pediatric hematology and oncology》1999,16(4):355-360
During 1993-1997, 247 cases of childhood acute leukemia (AL) were analyzed among inhabitants of the city of Kiev and Kiev region, excluding the most contaminated areas belonging to the strict control zone. The criteria of an FAB classification supplemented by immunophenotyping data were applied. The AL pattern was shown to be quite typical except for several peculiar features characteristic of this regional group of patients, especially the absence of age peaks in children with acute myelogenous leukemias (AML), increased frequency of the T1 variant in T-cell acute lymphoblastic leukemia (ALL), and higher levels of M4 and M5 variants in AML. A typical variant of M5a-AML with minimal signs of differentiation was found. 相似文献
6.
Maria G. Motlagh Liliya Katsovich Nancy Thompson Haiqun Lin Young-Shin Kim Lawrence Scahill Paul J. Lombroso Robert A. King Bradley S. Peterson James F. Leckman 《European child & adolescent psychiatry》2010,19(10):755-764
Attention-deficit/hyperactivity disorder (ADHD) is frequently diagnosed in children with Tourette syndrome (TS). The basis
for this co-occurrence is uncertain. This study aimed to determine if specific pre- and perinatal risk factors, including
heavy maternal smoking and severe psychosocial stress during pregnancy, were associated with one or both disorders, or neither.
We compared maternal report data on pre- and perinatal risk factors on 222 children between the ages of 7 and 18 years including
45 individuals with TS alone, 52 individuals with ADHD alone, 60 individuals with condition of comorbid TS + ADHD, and 65
unaffected control children. Pre- and perinatal histories as well as psychiatric assessments were performed using standardized
questionnaires and semi-structured interviews with the mothers and children. Logistic regression was used to determine the
odds ratio for each variable of interest. Compared to the mothers of unaffected control children, the mothers of children
with ADHD alone reported higher rates of heavy smoking (>10 cigarettes per day) during pregnancy and higher levels of severe
psychosocial stress during pregnancy (OR = 13.5, p < 0.01 and OR = 6.8, p < 0.002, respectively). The TS + ADHD and the TS alone patients also had higher rates heavy maternal smoking and high levels
of psychosocial stress compared to the control children, but these differences failed to reach statistical significance (heavy
smoking: OR = 8.5, p < 0.052, OR = 4.6, p < 0.19, respectively; severe psychosocial stress: OR = 3.1, p < 0.07, OR = 2.6, p < 0.11, respectively). Heavy maternal smoking and severe levels psychosocial stress during pregnancy were independently associated
with a diagnosis of ADHD. TS patients also had higher rates of these risk factors, but the ORs failed to reach statistical
significance. Efforts are needed to reduce the frequency of these risk factors in high-risk populations. Future studies, using
genetically sensitive designs, are also needed to sort out the causal pathways. 相似文献
7.
Gryshkova V Lituiev D Savinska L Ovcharenko G Gout I Filonenko V Kiyamova R 《Hybridoma (2005)》2011,30(1):37-42
Tumor-associated antigen MX35, which is overexpressed in 70-90% of epithelial ovarian cancers, has been recently identified as phosphate transporter NaPi2b. This finding has raised significant interest in understanding NaPi2b function under physiological conditions and its deregulation in human pathologies, such as cancer. As a member of the sodium-dependent phosphate transporter family, NaPi2b is primarily involved in the maintenance of phosphate homeostasis in the human body. The role of NaPi2b in oncogenic transformation and malignant growth is not well understood. To date, several monoclonal antibodies specific to NaPi2b have been reported. However, available monoclonal antibodies are not very efficient in recognizing endogenous NaPi2b under reducing conditions. In addition, these antibodies could not recognize the mutant form of transporter (NaPi2b-T330V). In this study we describe the production of monoclonal antibodies raised against the N-terminal region of NaPi2b. One of them, designated N-NaPi2b(15/1), possesses very useful immunological characteristics. We found that N-NaPi2b(15/1) specifically recognizes NaPi2b protein in immunohistochemical analysis and immunoprecipitation assay. Importantly, N-NaPi2b(15/1) antibody detects very efficiently endogenous and expressed wild-type and mutant forms of NaPi2b under both reducing and non-reducing conditions in Western blot analysis. These features make N-NaPi2b(15/1) antibody a very useful tool for studying the pattern of NaPi2b expression in health and pathologies. 相似文献
8.
9.
10.
The current study assessed whether activation of the novel estrogen receptor GPR30 ameliorates salt-dependent renal damage in intact mRen2.Lewis (mRen2) females. Hemizygous mRen2 rats were maintained on either a normal salt (0.5% Na) or high-salt (HS; 4.0% Na) diet for 10 weeks (5 to 15 weeks of age), and HS animals were treated with the GPR30 agonist G-1 or vehicle for 2 weeks. Systolic blood pressure markedly increased with HS diet (149±3 to 219±5 mm Hg; P<0.01), but G-1 did not influence pressure (P=0.42). G-1 and estradiol induced relaxation of preconstricted mesenteric vessels from normal salt mRen2 rats, but both responses were attenuated in the HS group. Despite the lack of an effect on blood pressure, G-1 decreased renal hypertrophy, proteinuria, urinary 8-isoprostane excretion, and tubular 4-hydroxynonenal staining. HS diet significantly increased GPR30 mRNA (1.01±0.04 versus 1.59±0.13; P<0.01) and protein (0.60±0.31 versus 3.99±0.75; P<0.01) in the renal cortex. GPR30 was highly expressed in the brush border of proximal tubules and colocalized with megalin. Finally, megalin expression was reduced by HS diet and restored with G-1. We conclude that GPR30-mediated beneficial effects in salt-sensitive mRen2 females occurred independent of changes in systolic blood pressure. The failure of G-1 to influence pressure may reflect a salt-induced impairment in GPR30-mediated vasorelaxation. The renoprotective actions of GPR30 may involve attenuation of tubular oxidative stress and activation of megalin-mediated protein reabsorption. 相似文献