全文获取类型
收费全文 | 107篇 |
免费 | 3篇 |
国内免费 | 4篇 |
专业分类
电工技术 | 1篇 |
化学工业 | 59篇 |
金属工艺 | 4篇 |
机械仪表 | 1篇 |
建筑科学 | 2篇 |
轻工业 | 2篇 |
无线电 | 1篇 |
一般工业技术 | 2篇 |
冶金工业 | 33篇 |
原子能技术 | 4篇 |
自动化技术 | 5篇 |
出版年
2022年 | 9篇 |
2021年 | 26篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2015年 | 2篇 |
2014年 | 3篇 |
2013年 | 5篇 |
2012年 | 1篇 |
2011年 | 4篇 |
2010年 | 9篇 |
2009年 | 9篇 |
2008年 | 5篇 |
2007年 | 8篇 |
2006年 | 6篇 |
2005年 | 6篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1994年 | 1篇 |
排序方式: 共有114条查询结果,搜索用时 62 毫秒
101.
目的 观察吗啡依赖戒断时大鼠脊髓和脑干μ受体和κ受体 mRNA 表达以及毒蕈碱受体拮抗剂 、 NMDA 受体拮抗剂和 NOS 抑制剂对这些基因表达的影响 。方法 用逆转录聚合酶链反应(RT -PCR),以β-actin mRNA 为内标检测μ受体和κ受体 mRNA 的表达水平 。结果 吗啡依赖大鼠脊髓和脑干μ受体 mRNA 表达明显升高,纳洛酮激发大鼠戒断反应 1h 后μ受体基因表达降低,4h 后接近正常组,而脊髓和脑干κ受体基因的变化与μ受体基因表达趋势相反 。鞘内注射 PKA 抑制剂 Rp-cAMPs 和蛋白磷酸酶抑制剂 calyculin A 可以明显减少脊髓和脑干中μ受体和κ受体基因表达,而 PKA 激活剂 Sp-cAMPs 则无明显影响;经 NOS 抑制剂 l-N-硝基精氨酸甲酯(l-NAME)处理后,脊髓μ受体和κ受体基因表达明显减少,经毒蕈碱(M)受体拮抗剂甲基东莨菪碱处理后,脊髓μ受体和脑干κ受体基因表达也明显减少,而脊髓κ受体和脑干μ受体基因表达变化不明显;经 NMDA 拮抗剂 MK801和 M1受体拮抗剂哌拉唑嗪处理后,脊髓和脑干μ受体和κ受体基因表达较戒断 1h 组无明显差异 。脊髓和脑干中β-actin 基因表达各处理组之间没有差别。结论 吗啡依赖和戒断动物脊髓和脑干中μ受体和κ受体基因表达发生改变,M受体拮抗剂和 NOS 抑制剂在吗啡戒断反应时减少μ受体和κ受体基因表达可能是它们有效控制吗啡戒断症状的机制之一 。 相似文献
102.
设计并合成了化合物1 烯丙基 6 氯 7 甲基 1,4 二氢喹喔啉 2,3 二酮,该化合物主要用于一系列新型NMDA受体拮抗剂的制备。反应以1 氯 4 氟 2 甲基苯为原料,在浓硫酸溶液中采用硝酸钾硝化得1 氯 4 氟 2 甲基 5 硝基苯,收率94 0%,将1 氯 4 氟 2 甲基 5 硝基苯与烯丙胺反应,三乙胺为缚酸剂,回流反应合成烯丙基 (4 氯 5 甲基 2 硝基 苯基) 胺,收率为81 0%,然后使用铁粉高收率还原所得的硝基化合物(收率为95 0%),再与二水合草酸在c(HCl)=2mol/L的盐酸中进行环合反应合成目的化合物1 烯丙基 6 氯 7 甲基 1,4 二氢喹喔啉 2,3 二酮(收率为90 6%),反应总收率为65 5%。 相似文献
103.
Marinelli L Cosconati S Steinbrecher T Limongelli V Bertamino A Novellino E Case DA 《ChemMedChem》2007,2(10):1498-1510
NMDA receptors are glutamate-gated ion channels (iGluRs) that are involved in several important physiological functions such as neuronal development, synaptic plasticity, learning, and memory. Among iGluRs, NMDA receptors have been perhaps the most actively investigated for their role in chronic neurodegeneration such as Alzheimer's, Parkinson's, and Huntington's diseases. Recent studies have shown that the NTD of subunit NR2B modulates ion channel gating through the binding of allosteric modulators such as the prototypical compound ifenprodil. In the present paper, the construction of a three-dimensional model for the NR2B modulatory domain is described and docking calculations allow, for the first time, definition of the ifenprodil binding pose at an atomic level and fully explain all the available structure-activity relationships. Moreover, in an attempt to add further insight into the ifenprodil mechanism of action, as it is not completely clear if it binds and stabilizes an open or a closed conformation of the NR2B modulatory domain, a matter, which is fundamental for the rational design of NMDA antagonists, MD simulations followed by an MM-PBSA analysis were performed. These calculations reveal that the closed conformation of the R1-R2 domain, rather than the open, constitutes the high affinity binding site for ifenprodil and that a profound stabilization of the closed conformation upon ifenprodil binding occurs. Thus, for a rational design and/or for virtual screening experiments, the closed conformation of the R1-R2 domain should be taken into account and our 3D model can provide valuable hints for the design of NR2B-selective antagonists. 相似文献
104.
NMDA受体(N-methyl-D-aspartate receptor)是离子型谷氨酸受体(ionotropic glutamate receptors,iGluRs)的一亚型,对谷氨酸的神经兴奋毒性起关键性作用,因此对于NMDA受体拮抗剂的应用已引起广泛重视。本研究选用NMDA受体甘氨酸位点拮抗剂1,4-二氢喹喔啉-2,3-二酮衍生物(QXs)为研究对象,采用比较分子场分析法(CoMFA)建立34个NMDA受体拮抗剂的三维定量构效关系(3D-QSAR)模型。此CoMA模型的交叉验证相关系数(q~2)0.566,最佳主成分数(ONC)6,非交叉验证相关系数(r~2)0.969,标准方差(SEE)0.236,立体场和静电场贡献值分别为62.3%和37.7%,研究结果可用分子场等势图直观表示。分子场等势图结果表明,在1,4-二氢喹喔啉-2,3-二酮衍生物苯环2,3位,减少取代基体积或增加取代基的正电性,可以提高该类化合物的活性。所建模型的预测能力和拟合能力较好,不仅了解清楚NMDA受体非竞争性拮抗剂的结构特征,还为设计活性更高的受体拮抗剂提供理论依据。 相似文献
105.
Muhia Mary; Feldon Joram; Knuesel Irene; Yee Benjamin K. 《Canadian Metallurgical Quarterly》2009,123(5):1114
The synaptic Ras/Rap-GTPase-activating protein (SynGAP) regulates specific intracellular events following N-methyl-d-aspartate receptor (NMDAR) activation. Here, the impact of SynGAP heterozygous knockout (SG+/?) on NMDAR-dependent functions was assessed using different positive reinforcement schedules in instrumental conditioning. The knockout did not affect the temporal control of operant responding under a fixed interval (FI) schedule, but led to a putative enhancement in response vigor and/or disinhibition. When examined on differential reinforcement of low rates of response (DRL) schedules, SG+/? mice showed increased responding under DRL-4s and DRL-8s, without impairing the response efficiency (total rewards/total lever presses) because both rewarded and nonrewarded presses were elevated. Motivation was unaffected as evaluated using a progressive ratio (PR) schedule. Yet, SG+/? mice persisted in responding during extinction at the end of PR training, although an equivalent phenotype was not evident in extinction learning following FI-20s training. This extinction phenotype is therefore schedule-specific and cannot be generalized to Pavlovian conditioning. In conclusion, constitutive SynGAP reduction increases vigor in the execution of learned operant behavior without compromising its temporal control, yielding effects readily distinguishable from NMDAR blockade. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
106.
Conti P Pinto A Tamborini L Grazioso G De Sarro G Bräuner-Osborne H Szabo G Gábor Hársing L De Micheli C 《ChemMedChem》2007,2(11):1639-1647
Homologation of the glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. We investigated the effects of a further increase in the distance between the amino acid moiety and the distal carboxylate group of model compounds (+/-)-1 and (+/-)-2 on their activity/selectivity profiles. We therefore synthesized new derivatives (+/-)-3-(+/-)-6, which are homologues of glutamic acid containing three additional carbon units. Moreover, because the potency of NMDA antagonists can be markedly increased by replacing the distal carboxylate with the bioisosteric phosphonate group, we also prepared the corresponding phosphonate derivatives (+/-)-7-(+/-)-10. All new compounds were submitted to binding assays with iGluRs, and derivatives (+/-)-3-(+/-)-6 were also tested in second messenger assays at representative mGluR subtypes. All the applied structural modifications were detrimental to the interaction with NMDA receptors. Conversely, structural variation of the nonselective mGluR ligand (+/-)-2 led to derivative (+/-)-5, which behaved as a selective group I metabotropic receptor antagonist. Notably, upon i.c.v. administration in DBA/2 mice, amino acid (+/-)-5 produced a significant protection against audiogenic seizures, whereas it was inactive after i.p. administration. 相似文献
107.
108.
Bonache MA García-Martínez C García de Diego L Carreño C Pérez de Vega MJ García-López MT Ferrer-Montiel A González-Muñiz R 《ChemMedChem》2006,1(4):429-438
The transient receptor potential vanilloid member 1 (TRPV1), an integrator of multiple pain-producing stimuli, is regarded nowadays as an important biological target for the discovery of novel analgesics. Here, we describe the first experimental evidence for the behavior of an old family of analgesic dipeptides, namely Xaa-Trp(Nps) and Trp(Nps)-Xaa (Xaa=Lys, Arg) derivatives, as potent TRPV1 channel blockers. We also report the synthesis and biological investigation of a series of new conformationally restricted Trp(Nps)-dipeptide derivatives with improved TRPV1/NMDA selectivity. Compound 15 b, which incorporates an N-terminal 2S-azetidine-derived Arg residue, was the most selective compound in this series. Collectively, a new family of TRPV1 channel blockers emerged from our results, although further modifications are required to fine-tune the potency/selectivity/toxicity balance. 相似文献
109.
110.
Alessandra Cazzaniga Giorgia Fedele Sara Castiglioni Jeanette A. Maier 《International journal of molecular sciences》2022,23(9)
Magnesium (Mg) is fundamental in the brain, where it regulates metabolism and neurotransmission and protects against neuroinflammation. To obtain insights into the molecular basis of Mg action in the brain, we investigated the effects of Mg in human brain organoids, a revolutionary 3D model to study neurobiology and neuropathology. In particular, brain organoids derived from human induced pluripotent stem cells were cultured in the presence or in the absence of an in vitro-generated blood–brain barrier (BBB), and then exposed to 1 or 5 mM concentrations of inorganic and organic Mg salts (Mg sulphate (MgSO4); Mg pidolate (MgPid)). We evaluated the modulation of NMDA and GABAergic receptors, and BDNF. Our data suggest that the presence of the BBB is essential for Mg to exert its effects on brain organoids, and that 5 mM of MgPid is more effective than MgSO4 in increasing the levels of GABA receptors and BDNF, and decreasing those of NMDA receptor. These results might illuminate novel pathways explaining the neuroprotective role of Mg. 相似文献