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A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.  相似文献   
3.
背景:原发性线粒体病具有高度的临床和遗传异质性,其中周围神经是线粒体病的常见受累器官之一。 目的:总结COX20基因变异相关周围神经病的临床表型及遗传学特征。 设计:病例系列报告。 方法:回顾性收集2018年5月至2020年5月复旦大学附属儿科医院诊治的COX20基因变异相关周围神经病患儿的临床资料,总结其临床表现、基因检测结果及治疗效果,并以“COX20”、“线粒体复合物Ⅳ缺乏症(Complex Ⅳ deficiency)”为关键词检索中英文数据库。检索时间均为从建库至2021年12月。总结已报道COX20基因变异与临床表型的关系。 主要结局指标:临床表型和COX20基因变异位点。 结果:4例患儿纳入分析,男、女各2例,其中3例自幼运动发育落后。4例均在儿童期起病,均以行走不稳为首发症状。肌电图均提示多发性周围神经损害改变,感觉神经轴索受累为主。4例患儿均携带COX20基因复合杂合变异,包括错义变异2个,无义变异和移码变异各1个,其中移码变异c.262delG(p.E88Kfs*35)尚未见报道。文献复习目前共报道COX基因变异18个家系22例患儿(包括本文病例),起病中位年龄为5(1.0~17)岁,22例均以行走困难或步态不稳起病,11例(50.0%)有精神运动发育迟滞,病程中14例(63.6%)出现构音障碍,14例(63.6%)出现肌力下降和/或足部畸形,8例(36.4%)出现共济失调,6例(27.3%)出现肌张力障碍,5例(22.7%)存在认知倒退等。21例患儿行神经传导及肌电图检查,19例(90.5%)提示多发性周围神经病变。头颅(18例)及脊髓(10例)MR检查提示,脊髓萎缩4例(40%),小脑萎缩4例(22.2%)。9例患儿已无法独立行走,丧失独立行走能力中位年龄为10(7~21)岁。目前共报道9个变异位点,4种变异类型,其中错义变异5个,剪切变异2个,无义变异和移码变异各1个。 结论:COX20基因变异患者多早期起病,以周围神经系统病变为主要表现,可合并构音障碍、共济失调、肌张力障碍、认知倒退等,病情逐渐进展,致残率高。COX20基因变异类型以错义变异最常见。  相似文献   
4.
缺血性心脏病日益危害着人们的健康,而恢复冠脉血流的首要治疗手段往往带来心肌缺血再灌注损伤(MIRI)。线粒体为心肌细胞提供大量能源,更参与调控细胞凋亡和信号转导等重要环节,在缺血缺氧环境中,受损线粒体会发生选择性、程序性自噬降解,以维持心肌细胞内环境稳态,该过程被称为线粒体自噬,与MIRI的发生发展密切相关。线粒体自噬具有双重性,准确有效地干预该水平对改善MIRI情况有着重要临床意义。近年来中医药在防治心血管疾病方面发挥了多靶点、多途径的治疗优势,逐步受到人们重视,越来越多的研究证实中药单体、组分、复方可通过保护线粒体结构及功能、调节线粒体自噬来挽救缺血心肌。探讨线粒体自噬在MIRI中的影响机制以及近年来中医药在此方面的研究进展,以期寻找以线粒体为治疗靶点的新策略。  相似文献   
5.
目的:探究Src羧基端激酶结合蛋白(csk-binding protein,CBP)在人肺癌组织中的表达水平,及其对线粒体分裂和自然杀伤(natural killer,NK)细胞杀伤肺癌细胞活性的影响。方法:免疫组织化学染色和实时荧光定量PCR(qRT-PCR)检测肺癌组织及癌旁组织中CBP的表达;含CBP慢病毒感染人肺癌细胞株A549,通过荧光倒置显微镜、qRT-PCR 和Western blot检测细胞感染效果;CCK-8法检测各组A549细胞活性,Mito-Tracker染色观察各组A549细胞内线粒体形态和长度变化,Western blot检测各组A549细胞线粒体动态相关蛋白Mfn1、Mfn2、Drp1的表达,免疫荧光染色检测各组A549细胞内细胞色素C(Cyt C)的表达,流式细胞术检测各组A549细胞凋亡情况;从人外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中分离NK细胞并进行鉴定,乳酸脱氢酶释放实验检测NK细胞对各组A549细胞的杀伤率。结果:肺癌组织中CBP的表达水平较癌旁组织中明显下降(P<0.01);感染CBP过表达慢病毒的A549细胞中CBP mRNA和蛋白的相对表达量均升高,培养48 h、72 h、96 h后细胞增殖活性下降,线粒体呈椭圆状或短杆状,长度明显缩短,线粒体分裂相关蛋白Mfn1、Mfn2蛋白表达减少,Drp1蛋白表达增加,有大量Cyt C从线粒体释放,细胞凋亡率升高,同时NK细胞对A549细胞的杀伤率明显提高,差异均具有统计学意义(P<0.01);而在使用线粒体分裂蛋白抑制剂Mdivi-1预先处理A549细胞后再感染CBP过表达慢病毒,线粒体分裂受到抑制,Mfn1、Mfn2蛋白表达增加,Drp1蛋白表达减少,Cyt C释放减少,细胞凋亡率降低,NK细胞对A549细胞的杀伤率也受到抑制,差异均具有统计学意义(P<0.01)。结论:CBP在人肺癌组织中低表达,在A549细胞中过表达CBP能够促进线粒体分裂与细胞凋亡,并提高NK细胞对A549细胞的杀伤率。  相似文献   
6.
肝再生的机制非常复杂,线粒体功能障碍所引起的能量供给不足是影响因素之一,但其机理亟待研究。严重肝损害时肝细胞ATP供应减少、线粒体能量代谢异常,导致肝再生受到抑制。补中益气汤为李东垣所创,其具补中益气、升阳举陷之功,有实验证实补中益气汤具有保护线粒体功能、增加线粒体能量代谢的作用,从而促进肝再生。本文综述补中益气汤总方与其中各类中药对线粒体能量代谢的保护作用,从而为促进肝再生提供新的治疗手段并对改善病人预后有重要意义。  相似文献   
7.
Frailty is a complex condition that emerges from dysregulation in multiple physiological systems. Increasing evidence suggests the potential role of age-related energy dysregulation as a key driver of frailty. Exercise is considered the most efficacious intervention to prevent and even ameliorate frailty as it up-tunes and improves the function of several related systems. However, the mechanisms and molecules responsible for these intersystem benefits are not fully understood. The skeletal muscle is considered a secretory organ with endocrine functions that can produce and secrete exercise-related molecules such as myokines. These molecules are cytokines and other peptides released by muscle fibers in response to acute and/or chronic exercise. The available evidence supports that several myokines can elicit autocrine, paracrine, or endocrine effects, partly mediating inter-organ crosstalk and also having a critical role in improving cardiovascular, metabolic, immune, and neurological health. This review describes the current evidence about the potential link between energy metabolism dysregulation and frailty and provides a theoretical framework for the potential role of myokines (via exercise) in counteracting frailty. It also summarizes the physiological role of selected myokines and their response to different acute and chronic exercise protocols in older adults.  相似文献   
8.
Although autosomal DNA testing has been available for a number of years, its use to reconstruct genetic profiles of people that lived centuries in the past is relatively recent and there are no published cases where it was employed to verify a kinship relation, likely to be an alleged paternity, that occurred one and a half century ago.DNA testing has already been employed to study the ancestry and posterity of Joseph Smith Jr., founder of the Latter-day Saint (Mormon) movement. Thanks to information found on the paternally inherited Y chromosome, a number of alleged paternities have been disproved, but obviously this analysis is not effective for alleged daughters. Likewise, his reconstructed mitogenome sequence, reported here for the first time, provides information about his maternal ancestry, but is useless in any paternity questions due to the strict maternal inheritance. Among all the children attributed to Joseph Smith Jr., Josephine Lyon, born in 1844, is perhaps the most frequently mentioned.In the current study, 56 individuals, mostly direct descendants of Joseph Smith Jr. and Josephine Lyon, had their autosomal DNA tested to verify Josephine’s biological paternity. Nearly 600,000 autosomal SNPs from each subject were typed and detailed genealogical data were compiled. The absence of shared DNA between Josephine’s grandson and Joseph Smith Jr.’s five great-grandchildren together with various amounts of autosomal DNA shared by the same individual with four other relatives of Windsor Lyon is a clear indication that Josephine was not related to the Smith, but to the Lyon’s family. These inferences were also verified using kinship analyses and likelihood ratio calculations.  相似文献   
9.
The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.  相似文献   
10.
Background: Skeletal muscle mitochondrial activity is reduced by?~?50–60% after SCI, resulting in impaired energy expenditure, glucose utilization and insulin sensitivity. Near infra-red spectroscopy (NIRS) is a non-invasive tool that can be used to assess mitochondrial capacity.

Objectives: (1) Highlight methodological limitations impacting data acquisition and analysis such as subcutaneous adipose tissue (SAT) thickness, movement artifacts, inadequate muscle stimulation, light interference, and ischemic discomfort. (2) Provide technical considerations to improve data acquisition and analysis. This may serve as guidance to other researchers and clinicians using NIRS.

Study Design: cross-sectional observational design.

Settings: Clinical research medical center.

Participants: Sixteen men with 1?>?year post motor complete SCI.

Methods: NIRS signals were obtained from right vastus lateralis muscle utilizing a portable system. Signals were fit to a mono-exponential curve.

Outcome Measures: Rate constant and r 2 values for the fit curve, indirectly measures mitochondrial capacity.

Results: Only four participants produced data with accepted rate constants of 0.002–0.013?s?1 and r 2 of 0.71–0.87. Applications of studentized residuals ≥2.5 resulted in sparing data from another four participants with rate constants of 0.010–0.018?s?1and r 2 values ranging from 0.86–0.99.

Conclusions: Several limitations may challenge the use of NIRS to assess mitochondrial capacity after SCI. Acknowledging these limitations and applying additional data processing techniques may overcome the discussed limitations and facilitate data sparing.  相似文献   
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