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1.
INTRODUCTIONThemicrotubule-associatedprotein蚲ishyperphos-phorylatedandglycosylatedinAlzheimerdisease(AD),andtheseabnormalmodificationsformedthebasisofprogressivelyretrogradeneurofibrillarydegenerationseeninADbrainandtherebythedementia(1,2).ADab-normallyphosphorylated蚲notonlyismicrotubuleas-semblyincompetent,butalsoinhibitsassemblyanddis-assemblesthepreassembledmicrotubulesinvitro(3).Inthetangle-bearingneuronsinADbrain,thenormalcytoskeletonisdisruptedandreplacedwi… 相似文献
2.
目的 探讨晕可宁颗粒的主要药效学 ,为临床提供药效学资料及治疗学基础。方法 采用三氯甲烷破坏豚鼠一侧膜迷路感受器模型 ,探讨受试药对眼震颤、摆头及旋转的影响 ;采用内淋巴囊和内淋巴管阻塞手术复制豚鼠膜迷路实验性膜迷路积水模型 ,研究内耳组织平均中阶面积 (SMA)增加率及形态学的变化。结果 抑眩宁阳性对照组、晕可宁颗粒 (8、16g/kg)模型给药组豚鼠眼球震颤次数减少 ,差异有显著意义 (P <0 .0 5 )。成功复制了不同程度膜迷路积水豚鼠模型 ,表现为前庭膜重度膨出 ,前庭阶缩小 ,膜蜗管增大 ,SMA增加率变大 ,差异有显著意义 (P <0 .0 1) ;晕可宁颗粒灌胃后可减轻豚鼠实验性膜迷路积水的程度 ,差异有显著意义 (P <0 .0 1) ;但与空白对照组比较SMA增加率差异无显著意义 (P >0 .0 5 )。结论 晕可宁颗粒可以减轻内淋巴囊积水程度 ,对梅尼埃病症状有对抗治疗作用。 相似文献
3.
Apolipoprotein B polymorphism and altered apolipoprotein B concentrations in Congolese blacks 总被引:1,自引:0,他引:1
Henri-Joseph Parra F. Martin F. Monard N. Ngangoué N. Copin J. M. Bard M. Qafli N. Vu Dac P. Duriez J. C. Fruchart 《Clinical genetics》1991,40(4):263-270
The immunoreactivity of apolipoprotein B (apo B) in plasma obtained from 238 unrelated black African male subjects from the People's Republic of Congo was analysed by non-competitive Enzyme Linked-Immunosorbent Assay (ELISA) with monoclonal BIP 45 anti-LDL antibody. The polymorphism detected by BIP 45 monoclonal antibody is identical to the Ag(c,g) polymorphism. Antibody BIP 45 distinguishes three apo B allotypes (immunophenotypes) encoded by the two allelic genes apo B Ag(c) and apo B Ag(g). Because of co-dominant transmission, genotypes may be inferred from allotypes, and it has been shown that BIP 45 binds strongly to the Ag(c) factor and only weakly to the allelic Ag(g) factor. Analysis of the Congolese plasma samples indicated that 67.65% of them bound BIP 45 with low affinity (Ag(c-,g+) genotype), 28.15% with intermediate affinity (Ag(c+,g+) genotype) and 4.20% with high affinity (Ag(c+,g-) genotype). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.817 and 0.183 for the type Ag(g)/Ag(c) alleles, respectively. After adjustment for age and body-mass index, it was found that the Ag(c) allele decreases the apo B level by 9.62 mg/dl and that the Ag(g) allele increases apo B by 0.43 mg/dl. Therefore, as much as 4.30% of the genetic variance for apo B level could be accounted for by the Ag(c,g) gene locus. 相似文献
4.
Mercury ingested from dietary sources has potent neurotoxic and teratogenic effects. Initial studies have shown that mercury may also affect fetal lung development. Since these pulmonary effects may play a role in subsequent neonatal morbidity and mortality due to compromising of the development of the lung, mercury effects in fetal and neonatal lung were investigated. Methylmercuric chloride (MMC), 1,000 ppm (15 mg/kg of body weight), was administered via an intragastric tube to timed-pregnant Swiss/Webster mice on day 9 of gestation. Lungs from fetuses on gestational day 18 and from neonates on days 1, 5, or 10 after birth were studied. Significant changes in MMC-exposed lungs compared to controls occurred at postnatal day 1. At this time, lung weight per gram body weight increased, phospholipid content per gram of lung or per microgram of DNA decreased, while DNA per gram of lung increased. Methylmercury appears to have delayed lung maturation. Cuboidal epithelial cells in alveolar tubules contained conspicuous glycogen deposits, and differentiation of alveolar type II cells was adversely affected. These results suggest that prenatal exposure to methylmercury may be detrimental to lung development, specifically to the initiation of surfactant synthesis, by delaying the normal pattern of maturation of the alveolar type II cells within the lungs. Pediatr Pulmonol. 1994; 17:11–21 . © 1994 Wiley-Liss. Inc. 相似文献
5.
男性不育患者精浆抗弓形虫IgG抗体与精子抗体关系的研究 总被引:1,自引:0,他引:1
目的:观察男性不育患者精浆中抗弓形虫 IgG 抗体。及其与抗精子抗体(AsAb)的关系。方法:采用 ELISA 方法测定169例男性不育患者及35例正常生育男性精浆抗弓形虫 IgG 抗体和 AsAb。结果:男性不育患者精浆抗弓形虫 IgG 抗体阳性率18.35%,显著高于正常生育组的2.86%(x~2=5.26,P<0.05)OR 为7.64;男性不育组精浆 AsAb 抗体阳性率为26.63%,也显著高于正常生育组(x~2=11.96,P<0.01)。精浆抗弓形虫抗体阳性的男性不育患者精浆AsAb 的阳性率为41.94%,与精浆抗弓形虫抗体阴性组的男性不育病人精浆 AsAb 的阳性率23.19%相比较,差异具有显著性(x~2=4.55,P<0.05).OR 为2.39。结论:男性不育患者精浆抗弓形虫抗体与精浆 AsAb 的产生可能有着一定的关系。 相似文献
6.
N. Limberger E. A. Singer K. Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1988,338(1):62-67
Summary Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic 2-autoreceptors of effects mediated by presynaptic opioid - and adenosine A1-receptors requires activation of the 2-receptors. The slices were preincubated with 3H-noradrenaline and then superfused with medium containing desipramine 1 mol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz.The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca2+-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 mol/l or yohimbine 0.3 mol/l. Ethylketocyclazocine (EK; 0.1–10 nmol/l) and R-(–)-N6-phenylisopropyladenosine (PIA; 1–1,000 nmol/1) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. — The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 mol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca2+ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine.The results demonstrate that there is no 2-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic 2-adrenoceptor does not interfere with presynaptic opioid - and adenosine A1-receptor mechanisms. It is only when the autoreceptor is activated by released noradrenaline that it attenuates neighbouring presynaptic receptor mechanisms, and this attenuation is removed by 2-adrenoceptor antagonists.Send offprint requests to N. Limberger at the above address 相似文献
7.
G. Molderings J. Likungu H. R. Zerkowski M. Gothert 《Naunyn-Schmiedeberg's archives of pharmacology》1988,337(4):408-414
Summary Spirally cut strips of human saphenous veins preincubated with 3H-noradrenaline were superfused in the presence of corticosterone and, unless stated otherwise, of cocaine or desipramine. Tritium overflow was stimulated electrically (2 Hz). Adrenaline (in the presence of rauwolscine), isoprenaline and the preferential 2-adrenoceptor agonist procaterol concentration-dependently increased the electrically evoked tritium overflow. Prenalterol, a -adrenoceptor agonist with moderate preference for 1-adrenoceptors, was ineffective. The concentration-response curve of isoprenaline was shifted to the right by the nonselective -adrenoceptor antagonist propranolol and by the preferential 2-adrenoceptor antagonist ICI 118,551, but was not affected by the 1-selective antagonist atenolol. In experiments on strips preexposed to adrenaline 10 nmol/l (i. e. a concentration higher than that which normally occurs in vivo) for 32 min in the absence of cocaine or desipramine, the electrically evoked 3H overflow was not affected 12 and 44 min after withdrawal of adrenaline, irrespective of whether propranolol was absent or present in the superfusion fluid. — In veins incubated with 3H-adrenaline, a considerable amount of the radioactivity was accumulated. During subsequent superfusion with 3H-adrenaline-free solution, electrical stimulation induced tritium overflow in a tetrodotoxin-sensitive manner. Propranolol failed to modify the evoked tritium overflow. — It is concluded that the sympathetic nerve fibres of the human saphenous vein are endowed with facilitatory presynaptic 2-adrenoceptors. These receptors do not seem to play a substantial role in a local adrenaline (previously taken up)-mediated positive feedback loop regulating noradrenergic transmission, at least under the present in vitro conditions.This study was supported by a grant of the Deutsche Forschungsgemeinschaft
Send offprint requests to M. Göthert 相似文献
8.
David de Wied Jan M. van Ree 《European archives of psychiatry and clinical neuroscience》1989,238(5-6):323-331
Summary Animal studies have demonstrated that neuropeptides modulate nervous system functions. It has been postulated that disturbances in neuropeptide systems may be aetiological factors in psychiatric and neurological disorders. Neuropeptides related to ACTH/MSH, including ORG 2766, increase motivation and attention and facilitate recovery processes after nerve damage. These peptides may be effective during the early stage of dementia. Vasopressin and related peptides improve memory processes in animals and humans. In addition, these peptides influence social behaviour, mood and addictive behaviour. The non-opioid -type endorphins have neurolepticlike activities in animals and antipsychotic effects in a category of schizophrenic patients. Peptides related to CCK have also been found to be effective in these patients. Some neuropeptides, e.g. TRH and PLG, have been reported to exert antidepressant effects. Further research may eventually produce neuropeptides with therapeutic action in psychiatric and neurological diseases.Parts of this article were presented on the occasion of the inauguration ceremony of the Department of Psychiatry of the University of Mainz on April 2 and 3, 1987 相似文献
9.
J. Gonçalves F. Carvalho S. Guimarães 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(3):288-292
Summary The present study was undertaken to compare the presynaptic interaction of neuronal noradrenaline uptake inhibitors with imidazoline and phenylethylamine 2adrenoceptor agonists under two different conditions: at low and high noradrenaline concentrations in the biophase.Isolated mouse vasa deferentia were stimulated with trains of 7 pulses given at 0.2 Hz and the inhibition by the 2-adrenoceptor agonists clonidine, -methylnoradrenaline, and UK-14,304 of twitch responses was measured in the absence and in the presence of either cocaine (12 mol/l) or desipramine (40 nmol/l). The effects were determined for the first (equivalent to single pulse stimulation) and the last stimulus of each train. Both uptake inhibitors antagonized the presynaptic inhibitory effects of imidazolines (clonidine and UK-14,304) on the last twitch; the effects on the first twitch remained unchanged. In contrast, the uptake inhibitors potentiated the inhibitory effect of the phenylethylamine (-methylnoradrenaline) on both the first and the last twitches.These results support the view that the concentration of noradrenaline in the biophase plays a decisive role in the inhibition by a2-adrenoceptor agonists of the electrically evoked release of noradrenaline. Agonists that are not substrates of neuronal uptake (i.e., clonidine, UK-14,304) become less effective when noradrenaline is present in the biophase while substrates of neuronal uptake (i. e., -methylnoradrenaline) do not. The results argue against the hypothesis that uptake inhibitors interact directly with presynaptic 2-adrenoceptors or act at some link between uptake and receptor sites.
Send offprint requests to S. Guimarães at the above address 相似文献
10.
The effects of clonidine and yohimbine on human information processing were tested in six normal volunteers ages 18–30 years. Subjects were tested in a pre-post design with sessions conducted at weekly intervals. Three drug conditions were: Placebo (lactose), 0.2 mg clonidine, and 30 mg yohimbine. Two choice reaction time (RT) tasks were used. One was a stimulus evaluation-response selection task (SERS) that has been shown to be sensitive tod-amphetamine, methylphenidate and scopolamine. The other task was to assess stimulus pre-processing and used spatial frequency as a discriminative stimulus. The principle finding was that clonidine slowed RT; this effect was significant for both tasks. In contrast, yohimbine tended to speed RT, but the effects were significant only for the spatial frequency task on some analyses while not for others. RTs to high spatial frequency stimuli were speeded more than for low spatial frequency. The effects of these two NE drugs were compared with findings withd-amphetamine and scopolamine and interpreted within the framework of a serial information processing model proposed by Callaway (1983). Specifically, it is suggested that yohimbine and clonidine affect an early pre-processing stage. 相似文献