全文获取类型
收费全文 | 185篇 |
免费 | 10篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 1篇 |
基础医学 | 13篇 |
口腔科学 | 21篇 |
临床医学 | 12篇 |
内科学 | 19篇 |
皮肤病学 | 5篇 |
神经病学 | 7篇 |
特种医学 | 1篇 |
外科学 | 4篇 |
综合类 | 26篇 |
预防医学 | 6篇 |
眼科学 | 1篇 |
药学 | 38篇 |
中国医学 | 21篇 |
肿瘤学 | 25篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 6篇 |
2015年 | 6篇 |
2014年 | 11篇 |
2013年 | 25篇 |
2012年 | 13篇 |
2011年 | 16篇 |
2010年 | 7篇 |
2009年 | 8篇 |
2008年 | 7篇 |
2007年 | 12篇 |
2006年 | 10篇 |
2005年 | 9篇 |
2004年 | 4篇 |
2003年 | 7篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 5篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1979年 | 1篇 |
排序方式: 共有202条查询结果,搜索用时 31 毫秒
1.
The Na+–Ca2+ exchange (NCX) system plays a pivotal role in regulating intracellular Ca2+ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca2+‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases. 相似文献
2.
从兔网织红细胞提纯的红细胞分化调节因子(erythroid differentiation factor,EDF),能对体外培养的自发转化成纤维细胞系L929及人鼻咽癌细胞系KB产生作用。当EDF剂量为0.10μg/ml时,可引起L929细胞形态发生改变,并有细胞核固缩现象。第2d的细胞生长抑制率为64.86%,软琼脂集落形成率为0;第5d时细胞增殖为负值。~3H-TdR掺入率明显降低。EDF剂量为0.15μg/ml时,对KB细胞生长已有抑制作用。EDF剂量达0.30μg/ml时,生长抑制明显。以上结果证明了EDF对恶性细胞具有增殖抑制作用。这种作用对不同种类细胞敏感性不同,并且与剂量呈正相关。 相似文献
3.
Thec mycproto oncogeneplaysaroleinmanycellularprocesses ,suchasproliferation ,differentiationandapoptosis Itisanearly responsegenenecessaryforcell cycleprogression (G1 Stransition)andactivatesquiescentcellsintothecellcycle (G0 G1transition) Down regulationofc … 相似文献
4.
《药学学报(英文版)》2017,7(5):564-570
Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy. 相似文献
5.
目的 评估纳米二氧化锆(nano-ZrO2)对人类口腔细胞活性的影响.方法 采用不同浓度的纳米ZrO2颗粒(0、10、30、60、100、150、250 μg·ml-1)对Human epidermoid carcinoma(KB)细胞分别进行24、48、72 h的染毒,应用MTT法检测细胞活性.结果 ①24、48 h低浓度纳米ZrO2染毒时KB细胞活性较高;②24、48 h高浓度nano-ZrO2染毒时没有对KB细胞的活性产生明显影响;③染毒72 h之后KB细胞活性没有发生显著变化,nano-ZrO2对KB细胞也不具有细胞毒性.结论 在适当浓度下,nano-ZrO2对KB细胞活性无明显毒作用. 相似文献
6.
Thomas J.H. Chen Ph.D. Amanda L.C. Chen Ph.D. Abdalla Bowirrat Ph.D. M.D. William B. Downs B.Sc. Margret A. Madigan B.S.N. 《Journal of psychoactive drugs》2013,45(2):108-127
Abstract This document presents evidence supporting the role of the KB220/KB220Z neuroadaptagens consisting of amino-acid neurotransmitter precursors and enkephalinase-catecholamine–methyl-transferase (COMT) inhibition therapy called Neuroadaptagen Amino Acid Therapy (NAAT) in brain reward function. It is becoming increasingly clear that this novel formulation is the first neuroadaptagen known to activate the brain reward circuitry. Ongoing research repeatedly confirms the numerous clinical effects that ultimately result in significant benefits for victims having genetic antecedents for all addictive, compulsive and impulsive behaviors. These behaviors are correctly classified under the rubric of “Reward Deficiency Syndrome” (RDS). We are proposing a novel addiction candidate gene map. We present preliminary findings in the United States using qEGG and in China using Functional Magnetic Resonance Imaging (fMRI) regarding the effects of oral NAAT on the activation of brain reward circuitry in victims of SUD. In unpublished data utilizing an fMRI 2X2 design at resting state, NAAT in comparison to placebo shows activation of the caudate brain region and potentially a smoothing out of heroin-induced putamen (a site for emotionality) abnormal connectivity. Although awaiting final analysis, if confirmed by ongoing studies in China coupled with published qEEG results in America, showing an increase in alpha and low beta, NAAT may be shown to impact treatment outcomes. 相似文献
7.
《Postgraduate medicine》2013,125(6):214-226
AbstractBackground: It is well established that in both food- and drug-addicted individuals there is “dopamine resistance” associated with the DRD2 gene A1 allele. Based on earlier studies, evidence is emerging wherein the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may play a significant role in the recovery of individuals with reward deficiency syndrome, including those addicted to psychoactive chemicals. Findings: Positive outcomes demonstrated by quantitative electroencephalographic (qEEG) imaging in a randomized, triple-blind, placebo-controlled, crossover study involving oral Synaptose Complex KB220Z? showed an increase of alpha waves and low beta wave activity in the parietal brain region. Using t statistics, significant differences observed between placebo and Synaptose Complex KB220Z? consistently occurred in the frontal regions after week 1 and then again after week 2 of analyses (P = 0.03). This is the first report to demonstrate involvement of the prefrontal cortex in the qEEG response to a natural putative D2 agonist (Synaptose Complex KB220Z?), especially evident in dopamine D2 A1 allele subjects. Independently, we have further supported this finding with an additional study of 3 serious polydrug abusers undergoing protracted abstinence who carried the DRD2 A1 allele. Significant qEEG differences were found between those who received 1 dose of placebo compared with those who were administered Synaptose Complex KB220Z?. Synaptose Complex KB220Z? induced positive regulation of the dysregulated electrical activity of the brain in these addicts. The results are indicative of a phase change from low amplitude or low power in the brain to a more regulated state by increasing an average of 6.169 mV2 across the prefrontal cortical region. In the first experiment we found that while 50% of the subjects carried the DRD2 A1 allele, 100% carried ≥ 1 risk allele. Specifically, based on the proposed addiction risk score for these 14 subjects, 72% had moderate-to-severe addiction risk. Similar findings were obtained by repeating the experiment in 3 additional currently abstinent polydrug abusers carrying the DRD2 A1 allele. Conclusion: This seminal work will provide important information that may ultimately lead to significant improvement in the recovery of individuals with psychostimulant and polydrug abuse problems, specifically those with genetically induced dopamine deficiency. Based on this small sample size, we are proposing that with necessary large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, we may eventually have the clinical ability to classify severity according to genotype and possession of risk alleles, along with offering a safe, nonaddicting, natural dopaminergic receptor agonist that potentially upregulates instead of downregulates dopaminergic receptors, preferably the D2 subtype. 相似文献
8.
Synthesis and preliminary evaluation of a 99mTc‐labeled folate‐PAMAM dendrimer for FR imaging 下载免费PDF全文
Manli Song Zhide Guo Mengna Gao Changrong Shi Duo Xu Linyi You Xiaowei Wu Xinhui Su Rongqiang Zhuang Weimin Pan Ting Liu Xianzhong Zhang 《Chemical biology & drug design》2017,89(5):755-761
Folate receptor is an ideal target for tumor‐specific diagnostic and therapeutic. The aim of this study was to synthesize 99mTc‐labeled folate‐polyamidoamine dendrimer modified with 2‐hydrazinonicotinic acid (99mTc‐HP 3FA ) for FR imaging. The 99mTc‐HP 3FA conjugate was prepared using N‐tris‐(hydroxymethyl)‐methylglycine and trisodium triphenylphosphine‐3,3′,3″‐trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro‐single‐photon emission computed tomography/CT imaging were performed. The radiolabeled 99mTc‐HP 3FA conjugate was prepared with high radiolabeling yield, good stability, and water solubility (logP = ?1.70 ± 0.21). In cell uptake study, the radiolabeled conjugate showed high uptakes in the FR ‐abundant KB cells and could be blocked significantly by excess folic acid. The 7721 cells which served as control group substantially had no uptakes. The results of micro‐single‐photon emission computed tomography/CT imaging exhibited that high accumulation of activity was found in FR ‐overexpressed KB tumor, and the tumor‐to‐muscle ratio was approximately 25.78, while, using free FA as inhibitor, the uptakes of 99mTc‐HP 3FA in KB tumor and kidney were obviously inhibited. In summary, a new radiocompound was synthesized successfully with specific FR targeting ability. The feasibility of 99mTc‐HP 3FA for early diagnosis of FR ‐positive tumors with non‐invasive single‐photon emission computed tomography imaging was demonstrated and the possibility of imaging‐guided drug delivery based on multifunctional polyamidoamine will be studied in the future. 相似文献
9.
目的獉獉:探讨脑源性神经营养因子(BDNF)是否作为核因子NF-κB的靶基因,参与NF-κB对可卡因行为敏化的影响。方法獉獉:建立NF-κB抑制剂DDTC作用下的小鼠可卡因诱导行为敏化模型,用Real-time PCR检测海马、前额叶皮质、伏隔核中Bdnf的表达。结果獉獉:可卡因可诱导伏隔核和海马(而非前额叶皮质)中Bdnf的上调,而在DDTC的作用下,总Bdnf及BdnfⅣ在伏隔核、海马和前额叶皮质中分别表达下调、不变和上调。结论獉獉:在不同的脑区NF-κB作用的机制可能不同,在伏隔核中,Bdnf可能作为NF-κB的靶基因参与可卡因行为敏化的形成。 相似文献
10.
目的:观察siRNA沉默口腔癌耐长春新碱细胞株KB/VCR细胞COX-2基因后,对KB/VCR细胞增殖及侵袭能力的影响。方法:将KB/VCR细胞分为COX-2 siRNA组、阴性对照组及空白对照组,采用RT-PCR检测各组细胞COX-2 mRNA的表达,蛋白印迹法检测COX-2蛋白的表达,MTT法检测各组细胞的生长抑制率,Transwell小室测定各组细胞侵袭能力的变化。结果:COX-2 siRNA组细胞的COX-2蛋白和mRNA的表达明显低于阴性对照组和空白对照组(P<0.01)。COX-2 siRNA组细胞的生长抑制率明显高于阴性对照组和空白对照组(P<0.01)。COX-2 siRNA组细胞的侵袭能力也明显降低。结论:COX-2 siRNA能特异性沉默KB/VCR细胞的COX-2基因,使KB/VCR细胞生长得到抑制,并减弱其侵袭能力。 相似文献