全文获取类型
收费全文 | 613篇 |
免费 | 32篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 17篇 |
妇产科学 | 2篇 |
基础医学 | 105篇 |
口腔科学 | 9篇 |
临床医学 | 27篇 |
内科学 | 49篇 |
皮肤病学 | 3篇 |
神经病学 | 164篇 |
特种医学 | 10篇 |
外科学 | 33篇 |
综合类 | 21篇 |
预防医学 | 13篇 |
眼科学 | 9篇 |
药学 | 169篇 |
中国医学 | 13篇 |
肿瘤学 | 4篇 |
出版年
2022年 | 6篇 |
2020年 | 7篇 |
2019年 | 9篇 |
2018年 | 5篇 |
2017年 | 6篇 |
2016年 | 2篇 |
2015年 | 13篇 |
2014年 | 17篇 |
2013年 | 22篇 |
2012年 | 12篇 |
2011年 | 21篇 |
2010年 | 22篇 |
2009年 | 34篇 |
2008年 | 43篇 |
2007年 | 24篇 |
2006年 | 32篇 |
2005年 | 20篇 |
2004年 | 22篇 |
2003年 | 27篇 |
2002年 | 18篇 |
2001年 | 17篇 |
2000年 | 23篇 |
1999年 | 12篇 |
1998年 | 19篇 |
1997年 | 21篇 |
1996年 | 23篇 |
1995年 | 12篇 |
1994年 | 16篇 |
1993年 | 15篇 |
1992年 | 12篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 12篇 |
1987年 | 12篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 4篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有652条查询结果,搜索用时 13 毫秒
1.
The objective of this investigation was to demonstrate the possible interactions of systemic lidocaine (lido) with inhibitory receptors in the spinal cord. In the lumbar dorsal horn of anesthetized and curarized rats, 60 physiologically identified, wide dynamic range (WDR) neurons, were recorded extracellularly. Glutamate, glycine and its selective antagonist, strychnine, were iontophoretically applied onto the neurons either singularly or concurrently. The effects of systemic lido on the drug-induced frequency changes and the interaction with the glycine receptors, using strychnine as a probe, were studied. It was consistently found that (i) lido (3–4 mg/kg) inhibited the excitatory responses to iontophoretic glutamate, (ii) this inhibition was significantly antagonized by concurrent iontophoretic strychnine, (iii) iontophoretic glycine induced comparable glutamate inhibition that was reversed by strychnine. In contrast, no effect on glutamate-induced excitations was observed when lido was applied by micropressure or a different local anesthetic was systemically administered. The results suggest that central inhibitory effects of lido could by mediated by spinal strychnine-sensitive glycine receptors, activated by lido itself or possibly by its glycine residue-bearing metabolites. 相似文献
2.
Glycine is thought ti be a major inhibitory neurotransmitter in the mammalian CNS. Two types of physiologically identified interneurons, Renshaw cells and Ia inhibitory interneurons, were intracellularly staind with horseradish peroxidase, and their axon terminals were studied at the electron microscopic level. Post-embedding immunogold procedures weer used to reveal the presence of glycine-like immunoreactivity. The synaptic terminals of both types of interneuron were significantly enriched with glycine-like immunoreactivity, providing support for the idea that glycine is a mediator of synaptic transmission in the recurrent and reciprocal inhibitory pathways to motoneurons. 相似文献
3.
Gerrit ten Bruggencate Udo Sonnhof 《Pflügers Archiv : European journal of physiology》1972,334(3):240-252
Summary Neutral ω-amino acids were applied iontophoretically in the hypoglossus nucleus. Intracellular recordings revealed inhibitory
actions involving hyperpolarization and conductance increase of the membrane. The antidromic field potential was reduced most
effectively by glycine, as judged by the comparison of iontophoretic currents. Picrotoxin, ejected electrophoretically, clearly
interfered with the action of GABA, glycine effects being reduced only with rather high currents. Strychnine had very specific
blocking ability against glycine actions.
Supported by the Deutsche Forschungsgemeinschaft (Br 242/7). 相似文献
4.
Svend Davanger Jon Storm-Mathisen Ole Petter Ottersen 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1994,98(2):342-354
Human retinae from surgical specimens rapidly fixed in a glutaraldehyde/formaldehyde mixture were subjected to postembedding, immunogold immunocytochemistry of glutamate and glycine, and subsequently analysed in an electron microscope. The two amino acids were visualised in the same tissue sections by the use of two different gold particle sizes. All bipolar cell perikarya and terminals showed significant glutamate labelling with mean gold particle densities 3–4 times higher than those of the retinal, non-neural pigment epithelial and Müller cells. Bipolar cell terminals displayed significantly higher glutamate labelling density than the bipolar cell bodies, as would be expected of glutamatergic neurons. A subpopulation of the glutamate-immunolabelled bipolar cell bodies (18%) and terminals (32%) also exhibited strong glycine labelling (7–8 times that of pigment epithelial and Müller cells). These glutamate-glycine positive terminals established contacts with amacrine cell processes and ganglion cell dendrites and were localised almost exclusively at between 44% and 88% depth of the inner plexiform layer, indicating that they belong to the ON cone bipolar system. This subpopulation of terminals was endowed with significantly higher glycine labelling density than the glycine positive bipolar cell bodies. These results show that human bipolar cell terminals colocalise glutamate and glycine and provide the first direct demonstration of an enrichment of these two amino acids in the same presynaptic element. 相似文献
5.
目的 :建立研究神经生理及药理的卵母细胞表达模型 ,并对鸡脑mRNA在卵母细胞上表达的氨基酸类受体进行研究。方法 :采用盐酸胍或异硫氰酸胍法抽提总RNA ,经寡聚脱氧胸苷 (oligo -dT)纤维素柱纯化得mRNA。mRNA微注射到卵母细胞内进行表达 ,以双电极电压钳技术研究表达的受体。结果 :模型能明显表达外源性mRNA表达的受体 ,而阴性对照无表达。在卵母细胞膜上表达的γ -氨基丁酸 (γ -aminobutyricacid ,GABA) ,甘氨酸(Glycine ,Gly)及红藻氨酸 (Kainate ,KA)受体 ,施加GABA ,Gly及KA均能引起一剂量依赖的内向电流 ,相应的拮抗剂可阻断其电流。剂量效应曲线显示GABA及KA诱导电流的半有效浓度 (EC5 0 )分别为 2 .9× 10 -5mol/L及 6 .3× 10 -5mol/L。结论 :卵母细胞可明显表达鸡脑mRNA编码的KA ,Gly及GABA受体 ,其药理特性与天然受体相似 ,是一个良好的神经生理及药理研究模型。 相似文献
6.
L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats 总被引:1,自引:1,他引:0
J. Konieczny Krystyna Ossowska Gert Schulze Helmut Coper Stanislaw Wolfarth 《Psychopharmacology》1999,143(3):235-243
Rationale: It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology
of Parkinson’s disease. Therefore, a search for new compounds which block glutamatergic receptors and show antiparkinsonian
properties in animal models of this disease seems to be justified. Objective: The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective
and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like muscle rigidity and catalepsy
induced by haloperidol in rats. Methods: The muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic
(EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior muscles. Results: L-701,324 (2.5–40 mg/kg IP) dose-dependently decreased the muscle tone enhanced by haloperidol (1–5 mg/kg IP). Likewise, the
haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost
abolished by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5
mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25–5 mg/kg IP) given alone or together with haloperidol (0.5–1 mg/kg IP)
disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to
or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed
balance and loss of control over their hind limbs. Conclusions: The present study suggests that L-701,324 exhibits a beneficial action in the animal model of parkinsonian rigidity, but not
that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects.
Received: 1 February 1998 / Final version: 20 October 1998 相似文献
7.
The transurethral resection syndrome 总被引:6,自引:0,他引:6
R. G. Hahn 《Acta anaesthesiologica Scandinavica》1991,35(7):557-567
The transurethral resection syndrome ("TUR syndrome") is caused by absorption of electrolyte-free irrigating fluid, and consists of symptoms from the circulatory and nervous systems. The clinical picture is inconsistent and the syndrome is easily confused with other acute disorders. Mild forms are common and often go undiagnosed, while severe forms of the TUR syndrome are rare and potentially life-threatening. The pathophysiology is complex but includes four mechanisms: circulatory distress from the rapid absorption of electrolyte-free irrigating fluid, adverse effects of glycine, dilution of the protein and electrolyte concentrations of the body fluids, and disturbance of renal function. The treatment of the TUR syndrome consists of general life support and in specific treatment directed towards hypotension, hyponatraemia and anuria. Methods to lower the uptake of irrigating fluid are widely used and probably reduce the incidence of the TUR syndrome. However, patient safety can be guaranteed only if the absorption is monitored. An irrigating fluid containing tracer amounts of ethanol can be used for this purpose. This permits the uptake of fluid to be indicated by measuring the concentration of ethanol in the patient's exhaled breath. 相似文献
8.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(7):645-659
The neurotransmitter glutamate is thought to be crucially involved in a huge number of neurological and psychiatric disorders, such as Morbus Parkinson, Alzheimer's disease and schizophrenia. Aiming at an improved diagnostic tool for PET a new [18F]fluorine labelled NMDA receptor ligand was developed that may potentially allow the in vivo visualization of glutama‐tergic neurotransmission. The 19F‐analogue trans‐5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydro quinoline‐2‐carboxylic acid was synthesised to determine the binding affinity, lipophilicity and biodistribution of the ligand. This substance exhibits a Ki of 12 nM for the glycine binding site using [3H]MDL‐105,519 assays on pig cortical membranes. A logD of 1.3 was determined for this compound according to the OECD guidelines employing the HPLC method. Radiosynthesis of this ligand was achieved by labelling the precursor trans‐5,7‐dichloro‐4‐[3‐(4‐piperazin‐1‐yl‐phenyl)‐ureido]‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid methyl ester with 2‐[18F]fluoroethyltosylate and subsequent cleaving of the methyl ester moiety, resulting in an overall decay corrected yield of 35% of the final product trans‐5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐[18F]fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid. The biodistribution kinetics of this compound were determined with Sprague Dawley rats ex vivo for brain, liver, kidney, and bone. The ligand showed a maximum brain uptake 30 min.p.i. of about 0.1% ID/g. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
9.
Bahram Mohammadi Klaus Krampfl Cener Cetinkaya Heiner Wolfes Reinhard Dengler Johannes Bufler 《Pharmacological research》2005,51(6):587-592
Glycine receptor channels are pentameric ligand-gated ion channels that respond to the application of inhibitory neurotransmitters by opening of a chloride-selective central pore. Topiramate (TPM) is a broad-spectrum antiepileptic drug used as add-on or monotherapy for focal seizures. In the present study the interaction of TPM with glycine receptor channels was studied on outside-out patches from HEK293 cells expressing alpha1beta glycine receptor channels. The patch clamp techniques combined with ultra fast solution exchange enabled us to investigate the kinetics of receptor channels in presence of TPM. Our study showed no agonistic or potentiating effect for TPM on glycine receptor channels. However, in presence of 1 mM glycine + 1 mM TPM, the desensitization got faster and the peak current amplitude decreased. After the end of glycine + TPM pulses, off-currents occurred, suggestive for a specific channel block mechanism. 相似文献
10.
目的 观察二甲氧乙二酰甘氨酸(DMOG)对小鼠缺血性急性肾衰竭的影响及其与低氧诱导因子1α(HIF-1α)活化之间的关系.方法 雄性C57/BL小鼠25只,随机分为5组:正常对照组(Control组),DMOG组(20 mg/kg,ip),假手术组(Sham组)及肾缺血-再灌注组(I/R组)和DMOG预处理组(DMOG+I/R组).采用夹闭双侧肾蒂30 min的方法建立小鼠缺血性急性.肾衰竭模型,DMOG注射6 h或缺血-再灌注24 h后采血并处死小鼠,全自动生化分析仪检测小鼠的肾功能,通过HE染色对肾组织病理学进行评分,免疫组织化学染色检测肾组织中波形蛋白的表达,TUNEL法检测细胞凋亡,Western blot方法检测肾HIF-1α活化情况.结果 DMOG组小鼠肾组织中HIF-1α的表达明显高于正常对照组(P<0.01);DMOG+I/R组小鼠.肾功能病理学评分明显低于I/R未处理组[BUN,(26.3±6.5) vs (65.8±2.6);Scr,(27.0±14.1) vs (229.5±11.2),P<0.01],DMOG+I/R组细胞凋亡程度和小管波形蛋白的表达较I/R组明显减少[(5.7±1.5) vs (23.3±2.1),P<0.05;(12.9±5.7) vs (69.6±22.7),P<0.01].结论 DMOG可通过诱导HIF-1α活化对缺血性急性肾衰竭小鼠发挥保护作用. 相似文献