全文获取类型
收费全文 | 239篇 |
免费 | 15篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 8篇 |
基础医学 | 26篇 |
临床医学 | 23篇 |
内科学 | 27篇 |
皮肤病学 | 2篇 |
神经病学 | 124篇 |
特种医学 | 13篇 |
外科学 | 7篇 |
综合类 | 13篇 |
预防医学 | 1篇 |
眼科学 | 4篇 |
药学 | 3篇 |
肿瘤学 | 1篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 7篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 14篇 |
2015年 | 5篇 |
2014年 | 10篇 |
2013年 | 8篇 |
2012年 | 9篇 |
2011年 | 11篇 |
2010年 | 14篇 |
2009年 | 7篇 |
2008年 | 19篇 |
2007年 | 9篇 |
2006年 | 8篇 |
2005年 | 5篇 |
2004年 | 6篇 |
2003年 | 8篇 |
2002年 | 5篇 |
2001年 | 5篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 13篇 |
1995年 | 8篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 6篇 |
1986年 | 1篇 |
排序方式: 共有256条查询结果,搜索用时 15 毫秒
1.
A case of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) which presented as migraine
complicated by stroke is reported. Strokes associated with migraine have often been reported, but the mechanism remains unclear
and may include a variety of pathologies. MELAS also presents with migrainous headache, vomiting, and stroke-like symptoms.
Magnetic resonance imaging demonstrates characteristic findings. MELAS should be considered in the differential diagnosis
of infarct-like lesions with migrainous headaches in young adults, especially if the symptoms fluctuate and are accompanied
by a homonymous hemianopia.
Received: 23 September 1996 Accepted: 19 February 1997 相似文献
2.
Akitomo Shimoji M.D. Shoichi Katsuragi M.D. Taihei Miyakawa M.D. Ryoichi Hira M.D. Kenjiro Watanabe M.D. Kohei Miyakawa M.D. Takateru Ishitsu M.D. Teruhisa Miike M.D. 《Psychiatry and clinical neurosciences》1987,41(1):47-55
Abstract: We report here two cases in a family with pleomorphic clinical features which include mitochondrial myopathy, encephalopathy, stroke-like episodes, episodic disturbances of consciousness and other multisystemic abnormalities. The other signs observed in multisystemic abnormalities were ophthalmoplegia, short stature, diabetes mellitus, diabetes insipidus, renal dysfunction, optic atrophy, retinal degeneration, impairment of hearing and mental retardation or deterioration. A symptomatological variation was observed in cases in the same family. It is suggested that these widely varying symptoms may be expressions caused by a common biochemical defect which involves different tissuesin different individuals in the family. The syndromes observed in the present cases were compared with other possibly-related mitochondrial encephalomyopathies. 相似文献
3.
Norio Ohkoshi Hldehlro Mizusawa Nobuko Shiraiwa Shin'Ichi Shoji Katsutoshi Harada Kazuo Yoshizawa 《Muscle & nerve》1995,18(11):1265-1271
Lmmunohistochemical analyses were made of the superoxide dismutases (Mn-SOD and CuiZn-SOD) in biopsied muscles from 7 patients with mitochondrial encephalomyopathies that included mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS), and chronic progressive external ophthalmoplegia (CPEO). Mn-SOD mainly was present in the subsarcolemmal region, but it also was found in a coarsely granular, reticular, or diffuse pattern of staining within the muscle fibers. These Mn-SOD-positive fibers corresponded almost completely to the ragged-red fibers. The immunoreaction for CuiZn-SOD was weakly positive in some of the muscle fibers positive for Mn-SOD. In CPEO, Mn-SOD-positive fibers predominantly showed decreased cytochrome c oxidase (COX) activity. In MELAS, Mn-SOD-positive fibers tended to be stained deeply for COX although a few were COX-negative. These findings suggest that Mn-SOD-positive fibers can be used to make a differential diagnosis between CPEO and MELAS and that in mitochondrial encephalomyopathies Mn-SOD in the raggedred fibers may protect against oxidative stress. © John Wiley & Sons, Inc. 相似文献
4.
In cybrid cells carrying the mitochondrial A3243G MELAS mutation, which were also heteroplasmic for the G12300A suppressor mutation, we observed a transient episode of heteroplasmic instability, resulting in a wide diversification in G12300A heteroplasmy levels and a shift in the average heteroplasmy level from 11 to 29%. These cells were found to be trisomic for chromosome 9, whereas a minority of cells that retained disomy-9 showed no instability. Coculture experiments implied that trisomy-9 cells exhibited a significant growth advantage, but neither heteroplasmy levels, respiratory phenotype nor trisomy-9 itself had direct selective value under standard culture conditions. Mitochondrial nucleoid number was the same (50–100) in cells that had or had not experienced transient heteroplasmic instability, but 1–2 orders of magnitude less than the segregation number in such cells. These findings support the idea that mtDNA partition is under nuclear genetic control, and implicate a locus on chromosome 9 in this regulation. 相似文献
5.
Xueli Chang Zhaoxu Yin Wei Zhang Jiaying Shi Chuanqiang Pu Qiang Shi Juan Wang Jing Zhang Li Yan Wenqu Yang Junhong Guo 《Medicine》2022,101(41)
The pathogenesis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS) syndrome has not been fully elucidated. The m.3243A > G mutation which is responsible for 80% MELAS patients affects proteins with undetermined functions. Therefore, we performed quantitative proteomic analysis on skeletal muscle specimens from MELAS patients. We recruited 10 patients with definitive MELAS and 10 age- and gender- matched controls. Proteomic analysis based on nanospray liquid chromatography-mass spectrometry (LC-MS) was performed using data-independent acquisition (DIA) method and differentially expressed proteins were revealed by bioinformatics analysis. We identified 128 differential proteins between MELAS and controls, including 68 down-regulated proteins and 60 up-regulated proteins. The differential proteins involved in oxidative stress were identified, including heat shock protein beta-1 (HSPB1), alpha-crystallin B chain (CRYAB), heme oxygenase 1 (HMOX1), glucose-6-phosphate dehydrogenase (G6PD) and selenoprotein P. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis showed significant enrichment in phagosome, ribosome and peroxisome proliferator-activated receptors (PPAR) signaling pathway. The imbalance between oxidative stress and antioxidant defense, the activation of autophagosomes, and the abnormal metabolism of mitochondrial ribosome proteins (MRPs) might play an important role in m.3243A > G MELAS. The combination of proteomic and bioinformatics analysis could contribute potential molecular networks to the pathogenesis of MELAS in a comprehensive manner. 相似文献
6.
A follow up study of myocardial involvement in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Heart (British Cardiac Society)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Objective—To investigate cardiac function in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and clarify the clinical features of cardiomyopathy in MELAS.
Patients—11 consecutive patients with MELAS (mean age at initial examination 11.3 years, range 4 to 16 years) were enrolled in the study. Six were followed for more than five years.
Results—On echocardiographic examination, three patients showed increased left ventricular end diastolic posterior wall thickness (LVPWTd), exceeding 140% of the normal value. Four patients, including these three, had an ejection fraction of less than 50%, and two also had increased left ventricular end diastolic volume (LVEDV) exceeding 140% of the normal value (%N). The LVPWTd%N was correlated positively with the LVEDV%N (R = 0.669, p < 0.05) and negatively with the ejection fraction (R = −0.6701, p < 0.05). One patient died of heart failure aged 22 years.
Conclusions—The cardiomyopathy in MELAS is characterised by an abnormally thick left ventricular wall with progressive dilatation and poor left ventricular contraction developing over several years, indicating hypertrophic cardiomyopathy advancing to dilated cardiomyopathy.
Keywords: MELAS; cardiomyopathy 相似文献
Patients—11 consecutive patients with MELAS (mean age at initial examination 11.3 years, range 4 to 16 years) were enrolled in the study. Six were followed for more than five years.
Results—On echocardiographic examination, three patients showed increased left ventricular end diastolic posterior wall thickness (LVPWTd), exceeding 140% of the normal value. Four patients, including these three, had an ejection fraction of less than 50%, and two also had increased left ventricular end diastolic volume (LVEDV) exceeding 140% of the normal value (%N). The LVPWTd%N was correlated positively with the LVEDV%N (R = 0.669, p < 0.05) and negatively with the ejection fraction (R = −0.6701, p < 0.05). One patient died of heart failure aged 22 years.
Conclusions—The cardiomyopathy in MELAS is characterised by an abnormally thick left ventricular wall with progressive dilatation and poor left ventricular contraction developing over several years, indicating hypertrophic cardiomyopathy advancing to dilated cardiomyopathy.
Keywords: MELAS; cardiomyopathy 相似文献
7.
K. G. Bensch W. deGraaf P. A. Hansen H. P. Zassenhaus J. A. Corbett 《Diabetes, obesity & metabolism》2007,9(S2):74-80
Low levels of somatic mutations accumulate in mitochondrial DNA (mtDNA) as we age; however, the pathogenic nature of these mutations is unknown. In contrast, mutational loads of >30% of mtDNA are associated with electron transport chain defects that result in mitochondrial diseases such as mitochondrial encephalopathy lactic acidosis and stroke-like episodes. Pancreatic β-cells may be extremely sensitive to the accumulation of mtDNA mutations, as insulin secretion requires the mitochondrial oxidation of glucose to CO2 . Type 2 diabetes arises when β-cells fail to compensate for the increased demand for insulin, and many type 2 diabetics progress to insulin dependence because of a loss of β-cell function or β-cell death. This loss of β-cell function/β-cell death has been attributed to the toxic effects of elevated levels of lipids and glucose resulting in the enhanced production of free radicals in β-cells. mtDNA, localized in close proximity to one of the major cellular sites of free radical production, comprises more than 95% coding sequences such that mutations result in changes in the coding sequence. It has long been known that mtDNA mutations accumulate with age; however, only recently have studies examined the influence of somatic mtDNA mutation accumulation on disease pathogenesis. This article will focus on the effects of low-level somatic mtDNA mutation accumulation on ageing, cardiovascular disease and diabetes. 相似文献
8.
M. Kishimoto Dr. M. Hashiramoto S. Araki Y. Ishida T. Kazumi F. Kanda M. Kasuga 《Diabetologia》1995,38(2):193-200
Summary We screened 214 Japanese NIDDM (non-insulin-dependent) diabetic patients with a family history of diabetes for mutations in the mitochondrial tRNALeu(UUR) gene using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Six patients were identified as having an A to G transition at position 3243 (3243 mutation), but no patients were detected with a T to C transition at position 3271, in the mitochondrial tRNALeu(UUR) gene. These two mutations were not present in 85 healthy control subjects. It was disclosed that the patients' mothers were also affected by diabetes mellitus in five of the six cases. In these six affected patients, the 3243 mutation shows variable phenotypes, such as the degree of multiple organ involvement, intrafamilial and interfamilial differences in disease characteristics, and the degree of the involvement of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) phenotype. Endocrinological examinations revealed that those diabetic patients with the 3243 mutation show not only beta-cell dysfunction, but also a defect in alpha-cell function, which is considered characteristic of diabetes with the 3243 mutation. When compared with 50 selected diabetic control subjects without the 3243 mutation, whose mothers, but not fathers, were found to have diabetes, it was established statistically that those with the 3243 mutation possess the following clinical characteristics; 1) the age of diabetes onset is lower, 2) they have lean body constitutions, and 3) they are more likely to be treated with insulin than control subjects. We suggest that diabetes with the 3243 mutation possesses phenotypes distinct from those in common forms of diabetes.Abbreviations NIDDM
non-insulin-dependent diabetes mellitus
- IDDM
insulin-dependent diabetes mellitus
- MELAS
mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
- PCR
polymerase chain reaction
- RFLP
restriction fragment length polymorphism
- BMI
body mass index
- ICA
islet cell antibody
- ICSA
islet cell surface antibody
- GAD
glutamic acid decarboxylase 相似文献
9.
Masahide Goto Hirofumi Komaki Takashi Saito Yoshiaki Saito Eiji Nakagawa Kenji Sugai Masayuki Sasaki Ichizo Nishino Yu-ichi Goto 《Brain & development》2014
The m.3302A>G mutation in the mitochondrial tRNALeu(UUR) gene has been identified in only 12 patients from 6 families, all manifesting adult-onset slowly progressive myopathy with minor central nervous system involvement. An 11-year-old boy presented with progressive proximal-dominant muscle weakness from age 7 years. At age 10, he developed recurrent stroke-like episodes. Mitochondrial myopathy, encephalopathy, lactic acidosis, plus stroke-like episodes (MELAS) was diagnosed by clinical symptoms and muscle biopsy findings. Mitochondrial gene analysis revealed a heteroplasmic m.3302A>G mutation. Histological examination showed strongly SDH reactive blood vessels (SSVs), not present in previous cases with myopathies due to the m.3302A>G mutation. These findings broaden the phenotypic spectrum of this mutation. 相似文献
10.
Martin-Kleiner I Pape-Medvidović E Pavlić-Renar I Metelko Z Kusec R Gabrilovac J Boranić M 《Acta diabetologica》2004,41(4):179-184
Abstract
In this work, patients having type 2 diabetes mellitus and diabetic mothers were tested for the presence of mitochondrial DNA point mutation A3243G. This mutation is associated with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), diabetes and deafness. Twenty-two diabetic persons were screened. DNA was isolated from peripheral blood lymphocytes and from swabs of oral mucosa. The mitochondrial DNA point mutation A3243G was detected using PCR-RFLP test. The mutation was detected in oral mucosal DNA of two patients (but not from lymphocyte DNA). One patient was a man with hearing and visual impairments and proteinuria; the other was a woman having proteinuria but no hearing impairment. The mutation was not detectable in oral mucosal DNA from the control persons: 20 diabetic patients having diabetic fathers and 22 healthy, nondiabetic volunteers. The incidence of mitochondrial DNA point mutation A3243G in this study of Croatian diabetic patients is in line with data in the literature. 相似文献