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581.
Epigenetic reprogramming and imprinting in origins of disease 总被引:2,自引:0,他引:2
The traditional view that gene and environment interactions control disease susceptibility can now be expanded to include
epigenetic reprogramming as a key determinant of origins of human disease. Currently, epigenetics is defined as heritable
changes in gene expression that do not alter DNA sequence but are mitotically and transgenerationally inheritable. Epigenetic
reprogramming is the process by which an organism’s genotype interacts with the environment to produce its phenotype and provides
a framework for explaining individual variations and the uniqueness of cells, tissues, or organs despite identical genetic
information. The main epigenetic mediators are histone modification, DNA methylation, and non-coding RNAs. They regulate crucial
cellular functions such as genome stability, X-chromosome inactivation, gene imprinting, and reprogramming of non-imprinting
genes, and work on developmental plasticity such that exposures to endogenous or exogenous factors during critical periods
permanently alter the structure or function of specific organ systems. Developmental epigenetics is believed to establish
“adaptive” phenotypes to meet the demands of the later-life environment. Resulting phenotypes that match predicted later-life
demands will promote health, while a high degree of mismatch will impede adaptability to later-life challenges and elevate
disease risk. The rapid introduction of synthetic chemicals, medical interventions, environmental pollutants, and lifestyle
choices, may result in conflict with the programmed adaptive changes made during early development, and explain the alarming
increases in some diseases. The recent identification of a significant number of epigenetically regulated genes in various
model systems has prepared the field to take on the challenge of characterizing distinct epigenomes related to various diseases.
Improvements in human health could then be redirected from curative care to personalized, preventive medicine based, in part,
on epigenetic markings etched in the “margins” of one’s genetic make-up. 相似文献
582.
海带多糖对心理应激大鼠血管内皮依赖性舒缩功能的影响 总被引:1,自引:0,他引:1
目的 研究海带多糖对心理应激大鼠血管内皮依赖性舒张和收缩功能的影响.方法 采用空瓶刺激法建立心理应激大鼠模型,大鼠随机分为对照组、模型组、海带多糖低剂量组、海带多糖高剂量组及低分子肝素组.经旷场试验后,取胸主动脉置于恒温灌流系统,分别记录血管环在累积浓度乙酰胆碱、去甲肾上腺素诱导后的血管舒缩反应,以及一氧化氮合酶抑制剂(左旋硝基精氨酸甲酯)孵育后累积浓度硝酸甘油的血管舒张反应情况.结果 模型组、海带多糖低剂量组、海带多糖高剂量组和低分子肝素组旷场行为学评分显著高于对照组(P<0.05).与对照组比较,模型组对乙酰胆碱诱导的血管舒张反应明显降低(P<0.05),对去甲肾上腺素诱导的血管收缩反应明显增强(P<0.05);与模型组比较,海带多糖高剂量组对乙酰胆碱诱导的血管舒张反应明显增强(P<0.05),对去甲肾上腺素引起的血管收缩反应明显减弱(P<0.05),海带多糖低剂量组和低分子肝素组血管舒缩反应无显著性变化(P>0.05).左旋硝基精氨酸甲酯孵育后,与对照组比较,模型组、海带多糖低剂量组、海带多糖高剂量组和低分子肝素组对硝酸甘油引起的舒张反应均显著降低(P<0.05),海带多糖高剂量组、海带多糖低剂量组和低分子肝素组加入左旋硝基精氨酸甲酯孵育后硝酸甘油诱导的血管最大舒张反应显著低于乙酰胆碱诱导(未加入左旋硝基精氨酸甲酯孵育)的血管最大舒张反应.结论 海带多糖对心理应激大鼠血管内皮依赖性舒缩功能具有保护作用.因此,海带多糖可以拮抗内源性肾上腺素增多导致的内皮损伤. 相似文献
583.
P. J. van der Schaar Y. Bremer C. B. H. W. Lamers A. A. M. Masclee 《Scandinavian journal of gastroenterology》2013,48(4):361-366
Background: Helicobacter pylori is a human gastric carcinogen. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. Cytotoxin-vacuolation toxin A (VacA) present in supernatants of H. pylori suspensions can cause gastritis and ulcer. The aim of this study was to examine the effects of H. pylori, ST and VacA in Mongolian gerbils. Methods: Male Mongolian gerbils (n = 196) were treated with H. pylori supernatants (10 ml/1000 mg) mixed with diet or inoculated intragastrically with H. pylori alone or with ST (100 or 1000 ppb), and then killed 27 months later. Gastric tissue sections were stained with haematoxylin and eosin (H&;E), periodic acid-Schiff (PAS), Alcian blue (AB, pH 2.5) and with immunostaining for PCNA and p53 expression. Results: In H. pylori-infected gerbils, the normal mucosa was replaced by hyperplastic epithelium. Severe gastritis, cystic dilatation of gastric glands, hyperplastic polyps and intestinal metaplasia were observed. In H. pylori + ST (1000 ppb) gerbils, intestinal metaplasia was significantly more frequent than in H. pylori alone animals. No pathological changes were observed in the H. pylori supernatant group. Osseous metaplasia was observed in the H. pylori + ST (100 ppb) group. Serum gastrin levels of the H. pylori + ST (1000 ppb) group were significantly higher than those of the other groups. PCNA labelling index and p53 index of infected gerbils were significantly higher than those of uninfected groups. Conclusion: H. pylori causes gastritis, ulcer and intestinal metaplasia. ST enhances the development of intestinal metaplasia and increases gastrin levels in H. pylori-infected Mongolian gerbils. 相似文献
584.
Provocation of Transient Lower Esophageal Sphincter Relaxations During Continuous Gastric Distension
J. W. A. Straathof M. M. van Veen A. A. M. Masclee 《Scandinavian journal of gastroenterology》2013,48(10):1140-1143
Background: Transient lower esophageal sphincter relaxations (TLESRs) are triggered by gastric distension. The aim of the study was to investigate TLESRs during controlled prolonged gastric distensions using the barostat technique. Methods: Twelve healthy volunteers (4 M, 8 F, age range 19-42 years) were studied under fasting conditions with combined esophageal manometry (Dentsleeve) and gastric barostat. Randomized isobaric distensions at 0 (control), 10, 12 and 14 mmHg were performed each period for 30 min with 30-min recovery periods in between. Results: The frequency of TLESR was significantly ( P < 0.05) higher during all distension periods compared to control periods (4.0 ± 0.4 TLESR/30 min versus 2.6 ± 0.4 TLESR/30 min). The frequency of TLESR in the first 15-min period of distension was significantly ( P < 0.001) higher compared to the second 15-min period pointing to adaptation (2.7 ± 0.3 TLESR/15 min versus 1.3 ± 0.2 TLESR/15 min, respectively). The frequency of TLESR correlated significantly with intragastric pressure ( r = 0.47; P < 0.01) and wall tension ( r = 0.48; P < 0.01), but not with intragastric volume. TLESR characteristics such as duration were not related to pressure or wall tension. Conclusions: Acute gastric distension increases the frequency of TLESR but adaptation occurs rapidly. The frequency of TLESR during distension is related to pressure and wall tension rather than to intragastric volume. 相似文献
585.
Daniela Pasquali Michele Arcopinto Andrea Renzullo Mario Rotondi Giacomo Accardo Andrea Salzano Daniela Esposito Lavinia Saldamarco Andrea M. Isidori Alberto M. Marra Antonio Ruvolo Raffaele Napoli Eduardo Bossone Andrea Lenzi Ragavendra R. Baliga Luigi Saccà Antonio Cittadini 《International journal of cardiology》2013
Background
Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter Syndrome (KS). Little information is available about the nature of the underlying cardiovascular abnormalities. Aim of the study was to investigate exercise performance, left ventricular architecture and function, vascular reactivity, and carotid intima-media thickness in a group of patients with KS.Materials and methods
Sixty-nine patients with KS and 48 age-matched controls participated in our population-controlled study. Forty-eight Klinefelter subjects were on testosterone treatment at the time of the investigation while 21 were naive and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test as well as a vascular study including measures of carotid intima-media thickness and endothelial function with flow-mediated dilation of the brachial artery. Patients with KS on testosterone therapy (n = 48) were also matched against a population of men with treated secondary hypogonadism (n = 21).Results
Patients with KS exhibited a wide array of cardiovascular abnormalities including left ventricular diastolic dysfunction, reduced maximal oxygen consumption (p < 0.01), increased intima-media thickness (p < 0.05) (− 34% and + 42% vs. controls, respectively) and a high prevalence of chronotropic incompetence (55% of patients, p < 0.01). No significant difference was found between treated and untreated KS in variance with men treated for secondary hypogonadism.Conclusion
Left ventricular diastolic dysfunction, impaired cardiopulmonary performance, chronotropic incompetence, and increased intima-media thickness suggest that cardiovascular abnormalities are a common finding in KS that is not reversed by testosterone replacement therapy and may represent the pathophysiological underpinnings of the increased risk of dying from heart disease. 相似文献586.
587.
588.
目的 探讨治疗性沟通护理联合放松疗法对支气管镜治疗患者的护理效果.方法 选取2018年8月至2019年8月于江南大学附属医院行支气管镜治疗的患者110例,按照双色球法随机分为两组.对照组接受常规护理干预,研究组增加治疗性沟通护理联合放松疗法干预,评估两组干预前后患者心理状况、支气管镜相关知识认知程度及生理指标变化.结果... 相似文献
589.