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1.
背景 利拉鲁肽在Ⅲ期临床试验中被证实可以有效降低糖尿病患者血糖水平,然而在临床应用过程中利拉鲁肽的降糖效果仍存在较大的个体差异。研究表明,基因多态性是造成众多药物出现个体差异的原因之一。目的 大麻素受体1型基因(CNR1)在糖尿病及其并发症中发挥重要作用,本研究旨在探讨CNR1多态性对利拉鲁肽治疗早期2型糖尿病(T2DM)患者临床疗效的影响。方法 选取2016年3月-2018年10月河南省直第三人民医院内分泌科收治的230例早期T2DM患者作为研究对象。患者均皮下注射利拉鲁肽进行治疗,治疗16周后测量体质指数(BMI)、空腹血糖(FPG)、餐后2 h血糖(2 hPG)和糖化血红蛋白(HbA1c)。另外,收集患者外周血及部分患者新鲜外周血标本分别用来进行CNR1基因1260G>A位点的基因分型及CNR1 mRNA的表达测定。结果 治疗16周后患者BMI、FPG、2 hPG、HbA1c水平均低于治疗前(P<0.05)。230例患者CNR1基因1260G>A位点的基因分型为:GG型188例(81.7%),GA型39例(17.0%),AA型3例(1.3%),最小等位基因频率为0.098,三种基因型分布频率符合哈迪温伯格平衡(P=0.550)。治疗16周后,GA/AA型患者BMI、FPG、HbA1c水平均低于GG型(P<0.05)。GG型和GA/AA型患者治疗16周后BMI、FPG、2 hPG、HbA1c水平均低于治疗前(P<0.05)。125例具有合适标本的CNR1 mRNA表达分析显示,GG型患者CNR1 mRNA表达水平高于GA/AA型患者(P<0.05)。不同基因型患者恶心呕吐、低血糖及总体不良反应发生率比较,差异均无统计学意义(P>0.05)。结论 利拉鲁肽在早期T2DM患者治疗中安全有效。CNR1基因1260G>A位点的GA/AA型可能通过影响该基因mRNA的表达进而影响利拉鲁肽对T2DM患者的疗效。  相似文献   
2.
Synthetic cannabinoids (SCs) are the most chemically diverse group of new psychoactive substances. This group has been associated with several intoxications, many with fatal outcomes. Although advancements have been achieved in pharmacology, metabolism, and detection of these compounds in recent years, these aspects are still unresolved for many SCs. The aim of this study was to investigate the in vitro potency of 14 indole‐ and indazole‐based SCs by applying a stable CB1 or CB2 receptor activation assay and correlating the activity with their structure. The half‐maximal effective concentration (EC50) of 5‐chloropentyl, 5‐bromopentyl, and 5‐iodopentyl JWH‐122 analogs varied from 74.1 to 283.7 nM for CB1 and 7.05 to 23.4 nM for CB2, where the addition of a chlorine atom enhanced the potency at CB1 compared with the bromo and iodo analogs. AM‐2201 was the most active at CB1 within this naphthoylindole family, with an EC50 of 23.5 nM but with the lowest efficacy (Emax 98.8%). Within the indole‐3‐carboxamide derivatives, 5F‐MDMB‐PICA was the most active compound, with a CB1/CB2 EC50 of 3.26/0.87 nM and an Emax around three times higher than JWH‐018. ADB‐FUBINACA was the most potent tested SC overall, with a CB1/CB2 EC50 of 0.69/0.59 nM, and an Emax around 3‐fold higher than that for JWH‐018 at CB1. The data obtained in this study confirm how small differences in the structure of SCs might lead to large differences in their activity, especially at CB1, which may be correlated with differences in their toxic effects in humans.  相似文献   
3.
Immune thrombocytopenia (ITP) is a heterogeneous disease which can be primary or secondary due to other conditions such as drugs. CB2 receptors (CB2R) also have a role in the ITP pathogenesis as CB2 receptor gene (CNR2) polymorphisms are associated with chronic immune thrombocytopenia and autoimmune diseases. K2 is synthetic marijuana which acts on cannabinoid receptors that are found on immune cells and thrombocytes. Here, we present a case who presented with ITP secondary to K2 usage and was successfully treated with 1?mg/kg prednisolone. This is the first ITP case in the literature due to K2. It is important in the era of the new drugs development of the CB2R mimetics.  相似文献   
4.
目的:探讨隔三七饼灸对佐剂诱导型类风湿性关节炎(RA)大鼠脊髓星形胶质细胞(AST)大麻素受体及促分裂原活化蛋白激酶(P38MAPK)表达的影响及作用机制。方法:采用足垫部皮下注射弗式完全佐剂(FAC)复制RA大鼠模型,将大鼠随机分为假手术组、隔三七饼灸治疗组(艾灸组)、模型组和红外线照射(TDP)治疗组(TDP组),每组10只,艾灸组取内膝眼、外膝眼、血海、足三里穴,予以隔三七饼灸治疗,每次每穴灸五壮,隔日1次,10次为1个疗程;TDP组予以TDP照射治疗,每次30分钟,隔日1次,10次为1个疗程;模型组、假手术组平行饲养,只在鼠板上固定而不作其他处理。在造模成功后、治疗一个疗程后分别观察记录踝关节疼痛试验评分、热痛阈和机械性痛阈,并采用免疫组织化学技术,观察大麻素受体CB1、CB2在脊髓背角的表达及P38MAPK在脊髓AST内表达。结果:造模后,与假手术组比较,模型组、艾灸组和TDP组大鼠的疼痛试验评分显著升高(P<0.01),热痛阈和机械痛阈显著降低(P<0.01);治疗1个疗程后,与模型组比较,艾灸组和TDP组的疼痛试验评分和P38MAPK的表达降低(P<0.01,P<0.05),热痛阈、机械痛阈以及CB1、CB2表达升高(P<0.01,P<0.05);与TDP组比较,艾灸组的疼痛试验评分和P38MAPK的表达明显降低(P<0.05),热痛阈、机械痛阈以及CB1、CB2表达明显升高(P<0.05)。结论:隔三七饼灸对RA大鼠产生的疼痛有良好的改善作用,能增强脊髓大麻素受体CB1、CB2表达,抑制P38MAPK的表达,其机制可能是艾灸通过调控脊髓大麻素受体CB1、CB2的表达,抑制P38MAPK的通路而对佐剂性关节炎产生镇痛作用。  相似文献   
5.
There is a growing body of evidence that cannabis may be effective as an analgesic with potential to reduce opioid usage in chronic pain. This review synthesizes the available literature to elucidate the possible role that cannabis might play in reducing opioid use in gynecological disorders that may potentially lead to a recommendation of substituting opioids with cannabis. With reports of a decrease in opioid use after cannabis initiation, an opioid-sparing effect has been seen in gynecologic malignancies such as ovarian, uterine, endometrial, and cervical cancers, in addition to chronic pelvic pain (CPP). Though many studies have found an association between cannabis and various adverse maternal and neonatal outcomes, there is a lack of randomized controlled trials making it difficult to claim a directly causal relationship between cannabis and these adverse outcomes. Additionally, with increased use of cannabis during pregnancy, the evidence of possible benefits and risks to mothers and fetuses is examined.  相似文献   
6.
Qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were developed and validated to screen and confirm the presence of nine phytocannabinoids in urine. The nine phytocannabinoids targeted in the methods included Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC, cannabidiol, 7-carboxy cannabidiol, cannabinol, cannabigerol, Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV. The methods presented use a rapid, single-step enzymatic hydrolysis followed by solid-phase extraction and LC-MS/MS analysis. Limits of detection were established at 1 µg/L for non-carboxylated analytes and 5 µg/L for carboxylated analytes. The screening and confirmation methods were validated and implemented in the analysis of authentic case samples. These methods can assist forensic, medicolegal, or medical compliance investigations as the presence of phytocannabinoids, or lack there-of, may be used to help differentiate cannabis (hemp, marijuana) use from synthetic THC (dronabinol) exposure.  相似文献   
7.
BackgroundMany inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation.ObjectiveIn order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation.MethodsThe effects of selected compounds on FcεRI-induced histamine and β-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited.ResultsWe found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen-dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine.ConclusionOur results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.  相似文献   
8.
《Seminars in immunology》2014,26(5):369-379
It has been well appreciated that the endocannabinoid system can regulate immune responses via the cannabinoid receptor 2 (CB2), which is primarily expressed by cells of the hematopoietic system. The endocannabinoid system is composed of receptors, ligands and enzymes controlling the synthesis and degradation of endocannabinoids. Along with endocannabinoids, both plant-derived and synthetic cannabinoids have been shown to bind to and signal through CB2 via G proteins leading to both inhibitory and stimulatory signals depending on the biological process. Because no cannabinoid ligand has been identified that only binds to CB2, the generation of mice deficient in CB2 has greatly expanded our knowledge of how CB2 contributes to immune cell development and function in health and disease. In regards to humans, genetic studies have associated CB2 with a variety of human diseases. Here, we review the endocannabinoid system with an emphasis on CB2 and its role in the immune system.  相似文献   
9.
Uncontrolled infection and increased inflammatory mediators might cause systemic inflammatory response. It is already known that Cannabinoid Type 2 (CB2) receptors, which are commonly expressed in immune cells and in many other tissues, have an effect on the regulation of immune response. In the present study of ours, the effects of CB2 receptor agonist JWH-133 was investigated on cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats. In the present study, Sprague-Dawley rats were divided into 5 groups (i.e. the Sham, CLP, JWH-133 0.2 mg/kg, JWH-133 1 mg/kg, and JWH-133 5 mg/kg Groups). Except for the Sham Group, the CLP-induced sepsis model was applied to all groups. The histopathological damage in brain, lung, liver and, heart was examined and the caspase-3, p-NF-κB, TNF-α, IL-1β and IL-6 levels were determined immunohistochemically. The serum TNF-α, IL-1β, IL-6, IL-10 levels were examined with the ELISA Method. The JWH-133 treatment decreased the histopathological damage in brain, heart, lung, and liver and reduced the caspase-3, p-NF-κB, TNF-α, IL-1β, IL-6 levels in these tissues. In addition to this, JWH-133 treatment also decreased the serum TNF-α, IL-1β, IL-6 levels, which were increased due to CLP, and increased the anti-inflammatory cytokine IL-10 levels. In the present study, it was determined that the CB2 receptor agonist JWH-133 decreases the CLP-induced inflammation, and reduces the damage in brain, lung, liver and heart. Our findings show the therapeutic potential of the activation of CB2 receptors with JWH-133 in sepsis.  相似文献   
10.
Irritable bowel syndrome (IBS) global burden is underestimated despite its high prevalence. It’s a gastrointestinal disease having obscure pathophysiology with multiple therapies yet unsatisfactory remedies. The Endocannabinoid system (ECS) of our body plays a key role in maintaining normal physiology of the gastrointestinal tract as well as involves abnormalities including functional diseases like IBS. This review highlights the importance of the Endocannabinoid system, its connections with the normal gastrointestinal functions and abnormalities like IBS. It also discusses the role of cannabis as medical therapy in IBS patients. A literature search for articles related to endocannabinoids in IBS and medical cannabis in PubMed and Google Scholar was conducted. The studies highlighted the significant participation of ECS in IBS. However, the breach in obtaining the promising therapeutic model for IBS needed further investigation in ECS and uncover other treatments for IBS. This review summarizes ECS, highlights the relationship of ECS with IBS and explores cannabis as a potential therapy to treat IBS.  相似文献   
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