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61.
Effects of mercury vapor inhalation on reactive oxygen species and antioxidant enzymes in rat brain and kidney are minimal 总被引:4,自引:0,他引:4
Metals are known to induce the formation of reactive oxygen species (ROS) that initiate oxidative stress, an important mechanism of cell injury. The brain is particularly sensitive to oxidative attack because of its high level of unsaturated lipids and high rate of oxidative metabolism. The objective of this study was to determine if elemental mercury (Hg(0)) vapor inhalation increases ROS production and affects activities or levels of antioxidant-related biomolecules in the rat brain and kidney. Adult female Sprague-Dawley rats were exposed for 2 h per day for 11 consecutive days to Hg(0) vapor (1, 2, and 4 mg Hg(0) m(-3)). Brain regions (frontal cortex, cerebellum, brain stem) and kidney were assayed for total Hg, ROS and glutathione (GSH) levels, and for enzyme activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). Marked exposure-related increases (2500-5600-fold) in total Hg were detected in the brain regions and in kidney. A statistically significant increase in ROS production (ca. 30% above controls) was observed only in the cortex of rats exposed to 1 mg m(-3) Hg vapor, but no significant changes were apparent at other exposures. Although a trend towards increasing ROS production was observed in the kidney, these effects were not statistically significant. Mercury vapor exposure had no significant effects on GSH levels or GPx activity in the three brain regions, however, statistically significant decreases in GSH and GPx activity were detected in the kidneys of rats exposed to 2 mg m(-3). Mercury exposure did not cause significant effects on SOD activity in the brain or kidney. The data indicate that oxidative stress and changes in GSH and activities of antioxidant enzymes do not play a major role in Hg(0) vapor toxicity in brain and kidney. 相似文献
62.
Bailey S Roberts A Brock C Price L Craft AW Kilkarni R Lee RE Skillen AW Skinner R 《British journal of cancer》2002,87(10):1092-1098
One aspect of concern for survivors of Wilms' tumour has been the late outcome in terms of renal function. Previous studies have documented low glomerular filtration rate and high blood pressure in some patients. Furthermore, disorders in tubular function (especially urinary concentration defects) have been suggested but not confirmed in small studies. The aim of this study was to determine the prevalence and nature of subclinical and overt glomerular, proximal and distal renal tubular toxicity in a population based cohort of survivors of Wilms' tumour. Forty patients (24 female) with a median age of 4.3 years (3 months-11.8 years) at diagnosis were studied. Median follow-up was 8.8 (range 0.06-27.5) years. Glomerular filtration rate was measured by (51)Cr-EDTA plasma clearance, proximal tubular function by electrolyte fractional excretions, urine excretion of low molecular weight proteins (retinol-binding protein) and renal tubular enzymes (alanine aminopeptidase; N-acetylglucosaminidase) and distal tubular function by the osmolality of the first two urines of the day on 3 consecutive days. Renal size (ultrasound) and blood pressure were also measured. Mean (range) glomerular filtration rate was 100 (61-150) ml min(-1) 1.73 m(-2). Nine were below the reference range for healthy individuals with two kidneys. Most serum electrolyte concentrations (sodium, potassium, chloride, calcium, magnesium and phosphate) fell within the normal range for age, as did the fractional excretions. The values that fell outside the normal range were only marginally abnormal. Subclinical measures of tubular toxicity (retinal-binding protein, alanine aminopeptidase, N-acetylglucosaminidase) were abnormal in only four patients. Thirty-seven patients achieved maximal urine osmolalities > or =800 mOsm kg(-1), but three failed to achieve this value even after DDAVP administration. Two patients had evidence of increased urinary albumin excretion. Compensatory renal hypertrophy was seen in all but two patients, but blood pressure was within normal limits in all patients. Current and past treatment for Wilms' tumour does not have any clinically important nephrotoxic effect in the majority of patients. This finding will enable paediatric oncologists to reassure patients and parents that treatment for Wilms' tumour rarely causes long-term renal impairment. 相似文献
63.
银杏黄酮对卡铂所致大鼠肾损害的防护作用 总被引:2,自引:0,他引:2
目的研究银杏黄酮(GBE)对卡铂(CBDCA)肾毒性的防护作用,并探讨其可能机制。方法灌胃给予大鼠GBE后腹腔内注射CBDCA,检测肾脏系数、血清尿素氮(BUN)及尿N-乙酰-β-D氨基葡萄糖苷酶(NAG)、血还原型谷胱甘肽(GSH)与肾皮质丙二醛(MDA)及线粒体谷胱甘肽过氧化酶(GSH-Px)及尿与肾皮质铂含量,观察GBE的防护作用的剂量依赖关系和经时过程。结果250、500和750mg/kgGBE预处理后第5天,CBDCA所致大鼠肾脏系数、NAG活性和BUN含量增高均不同程度减轻;500mg/kg组GBE预处理的效果最明显,该组肾脏系数、NAG活性和BUN含量分别为(0.79±0.12)g/100g、(15.86±3.28)U/gCre和(9.27±3.77)mmol/L,而CBDCA组这3项指标分别为(0.96±0.22)g/100g、(23.58±5.45)U/gCre和(31.08±15.00)mmol/L,上述各项指标两组间的差异有显著性(P<0.05或0.01)。GBE预处理可抑制CBDCA引起的MDA形成增高,GSH含量和GSH-Px活性下降,并能降低CBDCA所致大鼠肾皮质铂含量增高,促进铂经尿排泄。结论GBE有明显预防CBDCA的肾毒性,其部分机制为抗氧化作用,还可能与促进铂清除有关。 相似文献
64.
Prévot A Semama DS Justrabo E Guignard JP Escousse A Gouyon JB 《Pediatric nephrology (Berlin, Germany)》2000,14(5):370-375
Chronic cyclosporine A (CsA) nephrotoxicity has been widely assessed but only few studies have described acute nephrotoxicity.
As CsA is now used for short periods, we developed an experimental model of acute CsA-induced nephrotoxicity. Renal clearances
of inulin and para-aminohippurate were assessed in 35 New Zealand rabbits. Group 1: control, no treatment; group 2: CsA 25
mg/kg per day in 0.5 ml/kg per day for 5 days; group 3: vehicle Cremophor-EL, 0.5 ml/kg per day for 5 days; group 4: follow-up,
the same as group 2, then CsA discontinuation for 31 days. Compared with group 1, CsA significantly decreased glomerular filtration
rate (GFR), renal blood flow (RBF), and diuresis, with a significant increase in renal vascular resistance (RVR). The proportional
fall in GFR (–32.3%) and RBF (–33.1%) suggests both pre- and postglomerular vasoconstriction.Discontinuation of CsA in group
4 led to normalization of RVR with improvement of other renal function parameters. Compared with group 1, Cremophor-EL induced
no significant changes but an increased RBF. Microvacuolization of proximal tubule epithelial cells was the sole histological
abnormality observed only in group 2. The overall results suggest that CsA induced a vasomotor acute renal failure which was
not due to Cremophor-EL. This effect was partly reversible after discontinuation of treatment.
Received: 20 January 1999 / Revised: 24 June 1999 / Accepted: 13 August 1999 相似文献
65.
66.
目的:了解长期小剂量应用关木通是否可加重慢性肾衰竭大鼠肾脏损害。方法:采用5/6肾切除方法复制大鼠慢性肾衰竭模型,第1组给予与药典剂量相当(1g/kg)的关木通煎剂,第2组给予关木通3g/kg,第3组给予相同量的自来水,均每天灌胃1次,共8周,观察血清肌酐、尿素氮、尿蛋白含量以及肾脏形态变化。结果:8周后,第2组血清肌酐、尿素氮和尿蛋白排泄量显著高于第3组[分别为(165.0±15.6)和(109.8±10.0)μmol/L,(27.8±3.6)和(18.7±2.5)mmol/L,(68.2±10.1)和(44.6±8.5)mg/24h,P值均<0.05],肾间质病变和肾小球硬化程度也较重。结论:慢性肾衰竭大鼠对小剂量关木通的肾脏毒性作用的易感性增加,长期小剂量应用关木通可显著加速慢性肾衰大鼠肾脏损害进程。 相似文献
67.
三种纳米材料致大鼠肝肾损伤的初步研究 总被引:2,自引:0,他引:2
目的研究纳米二氧化硅(Nano-SiO2)、纳米四氧化三铁(Nano-Fe3O4)和单壁碳纳米管(SWCNTs)对大鼠肝、肾损伤作用。方法将42只雄性Wistar大鼠随机分为7组,分别为生理盐水对照组,以及3种纳米颗粒的高剂量组和低剂量组。灌胃染毒4周后处死大鼠,称肝、肾重量,计算肝、肾的脏器系数,测定大鼠血清某些生化指标,并对肝肾组织进行病理学观察。结果各染毒组肝、肾系数与对照组无明显差异;高剂量碳纳米管组碱性磷酸酶(ALP)活性以及高剂量碳纳米管组、高剂量纳米二氧化硅组天门冬氨酸氨基转移酶(AST)活性均较对照组增强(P<0.05);染毒组动物的肝细胞可见有脂肪变性,可见灶性及汇管区炎细胞浸润,各组间无明显差别,肾组织未见明显改变。结论本实验条件下3种纳米颗粒均可对大鼠肝脏产生一定程度损伤作用。 相似文献
68.
Irene Koneth Dominik Weishaupt Esther B Bachli 《Nephrology, dialysis, transplantation》2004,19(6):1654-1655
In February 2003, a study by Aspelin et al. [1] was publishedin the NEJM concerning reduced nephrotoxicity using the isoosmolarcontrast medium iodixanol in high risk patients. Case Recently, we performed a contrast-enhanced thoracic 16-channelmulti-slice computed tomography (CT) with intravenous (i.v.)administration of iodixanol 相似文献
69.
70.
M Nakamura T Itoh K Miyata T Uchisaka T Tanabe M Aono K Kimura 《Toxicology letters》1984,21(3):321-324
L-Alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) activities in urine are sensitive indicators of renal damage. However, urinary AAP loses its activity during storage in the frozen state. This study proposes a method for preventing the inactivation of AAP by adding glycerol to a final concentration of 10% to a urine sample before freezing and thawing. This study also showed that NAG is stable to freezing and thawing and is not affected by addition of glycerol. 相似文献