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1.

Aims

A long-term high-fat/cholesterol (HFC) diet leads to hepatic insulin resistance (IR), which is associated with autonomic dysfunction and cardiovascular diseases risk increasing. However, whether this occurs in Tibetan minipigs remains unknown. We tested that a long-term HFC diet caused hepatic IR and promote cardiovascular disorders in Tibetan minipigs, and are associated with the reduction of cardiovagal tone and baroreflex sensitivity (BRS).

Methods

Male Tibetan minipigs were fed either a standard diet or a HFC diet, and were euthanized at 12?weeks. Thereafter, the minipigs were tested for biochemical blood indices, glucose tolerance, blood pressure, heart rate variability (HRV), BRS, and insulin receptor substrate (IRS)-associated gene and protein expression levels, as well as cardiac function.

Results

HFC-fed minipigs developed IR by increasing body weight, total cholesterol, fasting blood glucose and insulin levels, and nonesterified fatty acid (NEFA) and high sensitive C-reactive protein (hs-CRP) levels, glucose intolerance. Increased adipose cell size, hepatic fat deposition, malondialdehyde (MDA) content and NEFA level, down-regulation of IRS1, IRS2, PI3K, Akt, p-Akt, Glut2 and PGC1ɑ expression concomitant with up-regulation of mTOR, GSK3β, TNF-ɑ, FOXO1, p-mTOR and p-p70S6K expression in the liver tissue, as well as hypertension and left ventricular diastolic dysfunction were observed in HFC-fed minipigs. HRV parameters and BRS values were further significantly reduced. Furthermore, multiple linear regression analysis showed that the development of hepatic IR toward cardiovascular disease was associated with low HFnu, RMSSD, BRS and LV ?dp/dtmax, high NEFA, high hepatic TG content.

Conclusion

These data suggest that HFC-fed Tibetan minipigs develop hepatic IR and promote cardiovascular disorders, and are associated with lower cardiovagal tone and BRS.  相似文献   
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慢性心力衰竭是一种复杂的心血管综合征,建立合适的慢性心力衰竭动物模型是研究慢性心力衰竭发病机制及相关药物治疗的关键。小型猪因其在病理生理、解剖结构等方面更接近人类,故建立小型猪慢性心力衰竭模型已成为研究热点。目前较成熟的小型猪慢性心力衰竭模型制备方法主要有心肌梗死型、前负荷过载型、后负荷过载型、药源型和心动过速型等。  相似文献   
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The Göttingen minipig is being used increasingly in biomedical research. The anatomical structure of the porcine peripheral nervous system has been extensively characterized, but no equivalent to the dermatome map, which is so valuable in human neurophysiological research, has been created. We characterized the medullar segmental skin and muscle innervations of the minipig hind body, using neurophysiological methodology. Six adult minipigs underwent unilateral laminectomy from L2 to S3, exposing the nerve roots. The skin of the hind part of the body was divided into 36 predefined fields, based on anatomical landmarks for consistent reproducibility. We recorded the evoked potential in each exposed nerve root L2‐S3 for cutaneous stimulation of each skin field, mapping the sensory innervation of the entire hind body. We subsequently recorded the motor response in seven predefined muscles during sequential stimulation of the L2‐S3 nerve roots. We obtained a clear sensory evoked potential in the nerve roots during stimulation of the skin fields, allowing us to map the sensory innervation of the minipig hind body. Neurophysiological data from skin stimulation and muscle recordings enabled us to map the sensory innervation of the Göttingen minipig hind body and provide information about muscular innervation. The skin fields were sensory innervated by more than one root. The muscles each had one dominant root with minor contribution from neighboring roots. This is consistent with experimental data from human studies.  相似文献   
6.
目的 探索一种适合小型猪牙种植实验的麻醉方法.方法 小型猪12只,随机均分为2组,单纯麻醉组采用陆眠宁Ⅱ0.2mL/kg肌肉注射,复合麻醉组采用陆眠宁Ⅱ联合氯胺酮0.2mL/kg肌肉注射(按1:1混合).观察麻醉显效时间、维持时间、苏醒时间并记录麻醉过程中体温、呼吸、心跳变化.结果 陆眠宁Ⅱ、氯胺酮复合麻醉组在麻醉显效时间、维持时间上优于陆眠宁Ⅱ单纯麻醉组,复合麻醉可以提高陆眠宁Ⅱ的麻醉效果,且用量较小,对心血管、呼吸无明显抑制.结论 陆眠宁Ⅱ、氯胺酮复合麻醉是小型猪牙种植实验理想的麻醉方法.  相似文献   
7.
ABSTRACT

Introduction: Influenza continues to be a major public health concern. Antivirals play an important role in limiting the burden of disease and preventing infection and/or transmission. The developments of such agents are heavily dependent on pre-clinical evaluation where animal models are used to answer questions that cannot be easily addressed in human clinical trials. There are numerous animal models available to study the potential benefits of influenza antivirals but each animal model has its own pros and cons.

Areas covered: In this review, the authors describe the advantages and disadvantages of using mice, ferrets, guinea pigs, cotton rats, golden hamsters and non-human primates to evaluate influenza therapeutics.

Expert opinion: Animals used for evaluating influenza therapeutics differ in their susceptibility to influenza virus infection, their ability to display clinical signs of illness following viral infection and in their practical requirements such as housing. Therefore, defining the scientific question being asked and the data output required will assist in selecting the most appropriate animal model.  相似文献   
8.
的确定成体西藏小型猪胰岛细胞体外分离、纯化的理想条件,为异种移植治疗糖尿病提供高质量的胰岛细胞。方法对比不同质量浓度的胶原酶(1mg/ml,2mg/ml,3mg/ml,4mg/m1)和同一质量浓度不同时间点(0min,15min,30min,45min,60min,75min,90min)分离获得胰岛细胞的数量和效果;使用Ficoll400密度梯度离心、淋巴分离液分离、离心和静置4种方法纯化胰岛细胞悬液,比较最终收集到的胰岛细胞数量和效果;用DTZ染色计算胰岛细胞的纯度;用AO/PI染色计算胰岛细胞存活率。结果确定了不同质量浓度的胶原酶获取胰岛细胞的最佳时间,胶原酶lmg/ml和2mg/ml组为45min,3mg/ml和4mg/ml组为30min,各组在最佳时间点获得胰岛细胞的数量最多的为1mg/ml组,胰岛细胞形态完整;4种纯化方法中,收集的胰岛细胞数量由多到少依次为静置组〉Ficoll400密度梯度离心组〉离心组〉淋巴分离液离心组。经AO/PI染色后检测胰岛细胞的存活率为95.00%以上。结论在组织块剪碎消化的情况下,胶原酶质量浓度lmg/ml、消化时间45min的分离条件可获得数量较多的胰岛细胞,Ficoll400密度梯度离心的纯化手段收集到的胰岛细胞效果最好。  相似文献   
9.
目的 分析比较四个品种小型猪的血液学生物学特性.方法 分别选取上海地区饲养的巴马小型猪、贵州小型猪和版纳小型猪及陆川小型猪,每个品种雌雄各20头,3~6月龄,测量其血液生理、血清生化与血凝指标,然后进行单因素方差分析,并进行数据比较.结果 四个品种的小型猪血液生理14个指标差异有统计学意义(P<0.05),血清生化12个指标组间差异有统计学意义(P<0.05),血凝4个指标差异都有统计学意义(P<0.05).分别对各品种群体数据进行比较分析,巴马小型猪群体雌雄间血液常规、血清生化和血凝指标差异显著(P<0.05)的指标分别有6项、4项和3项,而贵州小型猪、版纳小型猪和陆川小型猪雌雄间差异指标较少或差异不显著.四品种小型猪相同性别间比较,也有较多指标差异显著.结论 测定和比较的巴马小型猪、贵州小型猪、版纳小型猪和陆川小型猪在血液学、血清生化和血凝等方面数据,为应用和选择小型猪开展相关生物医学和药物研究提供了基础数据.  相似文献   
10.
目的:探讨海南五指山裸花紫珠(LHZZ)对鼻咽癌(NPC)细胞顺铂(DDP)诱导凋亡敏感性的影响,并探究其作用机制。方法:细胞增殖与活性检测(CCK-8)法检测不同浓度DDP(0,2,4,8,16,32 mg·L-1)和不同浓度海南五指山裸花紫珠(0,25,50,75,100 mg·L-1)处理后的细胞存活率。实验分组为空白组(正常HNE1细胞),DDP组(8 mg·L-1,24 h),LHZZ组(50 mg·L-1,24 h),DDP+LHZZ组(8 mg·L-1DDP+50 mg·L-1LHZZ,24 h),DDP+LHZZ+核因子E2相关因子2(Nrf2)激活剂莱菔硫烷(SFN)组(8 mg·L-1DDP+50 mg·L-1LHZZ,24 h;然后10μmol·L-1SFN,24 h),CCK-8法检测细胞存活率,集落克隆形成实验检测细胞集落形成能力,流式细胞术和原位末端标记法(TUNEL)染色检测细胞凋亡情况,荧光探针2',7'-二氯荧光黄双乙酸盐(DCFH-DA)检测培养细胞活性氧(ROS)水平,蛋白免疫印迹法(Western blot)检测细胞内凋亡相关蛋白B细胞淋巴瘤-2(Bcl-2),Bcl-2相关X蛋白(Bax)和半胱氨酸天冬氨酸蛋白水解酶-3(Caspase-3)表达,实时荧光定量聚合酶链式反应(Real-time PCR)检测细胞内Nrf2,抗氧化反应元件(ARE)mRNA表达。结果:与空白组比较,经过不同浓度DDP和不同浓度LHZZ处理后,细胞存活率均明显下降(P<0.05);与DDP组和LHZZ组比较,DDP+LHZZ组细胞存活率下降,细胞集落克隆形成数目减少,细胞凋亡水平升高,Bcl-2蛋白表达水平下调,Bax和Caspase-3蛋白表达水平则上调,差异具有统计学意义(P<0.05);而在DDP+LHZZ组中加入SFN激活Nrf2/ARE信号通路,上述效果均受到抑制(P<0.05)。此外,与空白组比较,LHZZ组细胞内ROS水平下调(P<0.05);与DDP组比较,DDP+LHZZ组ROS水平明显下调(P<0.05);与DDP+LHZZ组比较,DDP+LHZZ+SFN组细胞ROS水平明显上调(P<0.05)。结论:LHZZ可增加DDP诱导的鼻咽癌细胞凋亡的敏感性,其机制可能与阻断Nrf2/ARE信号通路并抑制ROS水平相关。  相似文献   
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