全文获取类型
收费全文 | 3893篇 |
免费 | 238篇 |
国内免费 | 56篇 |
专业分类
耳鼻咽喉 | 28篇 |
儿科学 | 46篇 |
妇产科学 | 15篇 |
基础医学 | 385篇 |
口腔科学 | 34篇 |
临床医学 | 130篇 |
内科学 | 285篇 |
皮肤病学 | 25篇 |
神经病学 | 162篇 |
特种医学 | 89篇 |
外科学 | 160篇 |
综合类 | 629篇 |
预防医学 | 103篇 |
眼科学 | 32篇 |
药学 | 909篇 |
1篇 | |
中国医学 | 1046篇 |
肿瘤学 | 108篇 |
出版年
2023年 | 74篇 |
2022年 | 118篇 |
2021年 | 151篇 |
2020年 | 135篇 |
2019年 | 106篇 |
2018年 | 79篇 |
2017年 | 117篇 |
2016年 | 96篇 |
2015年 | 91篇 |
2014年 | 194篇 |
2013年 | 175篇 |
2012年 | 216篇 |
2011年 | 183篇 |
2010年 | 132篇 |
2009年 | 107篇 |
2008年 | 107篇 |
2007年 | 95篇 |
2006年 | 87篇 |
2005年 | 143篇 |
2004年 | 152篇 |
2003年 | 146篇 |
2002年 | 67篇 |
2001年 | 98篇 |
2000年 | 61篇 |
1999年 | 66篇 |
1998年 | 53篇 |
1997年 | 34篇 |
1996年 | 45篇 |
1995年 | 67篇 |
1994年 | 48篇 |
1993年 | 42篇 |
1992年 | 44篇 |
1991年 | 46篇 |
1990年 | 43篇 |
1989年 | 48篇 |
1988年 | 53篇 |
1987年 | 58篇 |
1986年 | 40篇 |
1985年 | 66篇 |
1984年 | 63篇 |
1983年 | 44篇 |
1982年 | 41篇 |
1981年 | 64篇 |
1980年 | 60篇 |
1979年 | 45篇 |
1978年 | 38篇 |
1977年 | 27篇 |
1975年 | 17篇 |
1974年 | 20篇 |
1973年 | 17篇 |
排序方式: 共有4187条查询结果,搜索用时 19 毫秒
61.
C. Gramsch H. M. Emrich S. John S. Haas H. Beckmann M. Zaudig D. von Zerssen 《Journal of neural transmission (Vienna, Austria : 1996)》1984,60(2):133-141
Summary Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/ SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined. 相似文献
62.
Charles-Henri Malbert 《Nutrients》2021,13(2)
Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and comparative anatomy of the proximal part of the gut to that of humans, has provided several important insights relating to the relevance of vagally mediated gut-brain relationships to the regulation of food intake. Furthermore, its large size combined with the capacity to become obese while overeating a western diet makes it a pivotal addition to existing murine models, especially for translational studies relating to obesity. How gastric, proximal intestinal, and portal information relating to meal arrival and transit are encoded by vagal afferents and their further processing by primary and secondary brain projections are reviewed. Their peripheral and central plasticities in the context of obesity are emphasized. We also present recent insights derived from chronic stimulation of the abdominal vagi with specific reference to the modulation of mesolimbic structures and their role in the restoration of insulin sensitivity in the obese miniature pig model. 相似文献
63.
目的 分离纯化r-K4K5,探讨r-K4K5对牛毛血管内皮(BCE)细胞、鸡胚绒毛尿囊膜(CAM)新生血管生成及实验性人肺腺癌SPC-A1生长的抑制作用。方法 通过盐析、凝胶过滤提纯r-K4K5,BCE细胞在含r-K4K5的DMEM中培养24、48、72h后分别计数;孵化7d的鸡胚加r-K4K5后继续孵育72h,观察新生血管生成;已经接种入SPC-A1肺腺癌组织的荷瘤裸小鼠(Balb/c,nu/nu),瘤旁注射r-K4K5继续饲养,观察肿瘤生长变化。结果 r-K4K5抑制BCE细胞增殖,48~72h作用明显;r-K4K5处理的CAM组中直径小于50um的小血管明显减少;高剂量r-K4K5治疗的荷瘤裸小鼠组,平均瘤重与对照组比较有统计学意义。结论 r-K4K5能够抑制BCE细胞增殖,抑制鸡胚CAM新生血管生成,抑制实验性人SPC-A1肺腺瘤生长。 相似文献
64.
目的 优选经典名方华盖散基准样品的干燥方法。方法 采用真空干燥、真空带式干燥、喷雾干燥、冷冻干燥方法制备华盖散基准样品,应用扫描电子显微镜、差式扫描量热分析、HPLC等方法测定基准样品的质量属性,以得粉率、玻璃化转变温度及成分含量转移率等为评价指标,运用熵权法对各指标赋予权重进行综合评价。结果 喷雾干燥基准样品粒子呈类球形、粒径最小,冷冻干燥基准样品不规则、蓬松、溶化性好。指标成分盐酸麻黄总碱、苦杏仁苷、橙皮苷、甘草苷、甘草酸转移率分别为85.66%~104.78%、90.81%~104.16%、91.42%~94.86%、83.98%~94.69%、87.85%~94.45%,指纹图谱相似度均大于0.9。结论 经综合评价得出冷冻干燥方法最佳,3批验证工艺重复性、可行性较好,为经典名方基准样品质量属性研究提供了理论依据和实践价值。 相似文献
65.
目的 基于中医药整合药理学和转录组学探究丹栀逍遥散防治焦虑肝郁化火证的作用机制。方法 采用中医药整合药理学研究平台v2.0,检索并获取丹栀逍遥散的活性成分及靶标、焦虑肝郁化火证靶标信息,构建中药-成分-靶点-通路网络。将交集基因导入String数据库,构建交集靶点的蛋白互作网络,以确定最终需要验证的靶标。利用GEO数据库转录组学验证整合网络药理学结果,同时采用动物实验进行验证。结果 共筛选出与焦虑肝郁化火证相关的靶标13个,丹栀逍遥散活性成分430种。整合药理学结果显示,丹栀逍遥散防治焦虑肝郁化火证主要通过调控α-氨基-3-羟基-5-甲基-4-异噁唑丙酸受体(α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor,AMPAR)、蛋白激酶A(protein kinase A,PKA)、N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体的激活及磷脂酰肌醇3-激酶(phosphatidylinositide 3-kinases,PI3K)/蛋白激酶B(protein kinase B,... 相似文献
66.
Huang Tien L. Székács András Uematsu Tamon Kuwano Eiichi Parkinson Andrew Hammock Bruce D. 《Pharmaceutical research》1993,10(5):639-648
Thirty carbonates, thiocarbonates, carbamates, and carboxylic esters of -naphthol, -naphthol, and p-nitrophenol were synthesized and tested as substrates for liver carboxylesterases from the crude microsomal fractions of human and mouse, and purified isozymes, hydrolases A and B, from rat liver microsomes. The carbonates, thiocarbonates, and carboxylic esters of -naphthol were cleaved more rapidly than the corresponding -naphthol isomers by the mammalian liver esterases. -Naphthyl esters of acetic, propionic, and butyric acids were among the best substrates tested for these enzymes. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A, although the Michaelis–Menten constant (K
m) values of selected substrates differed widely with these two isozymes. Malathion was a 15-fold better substrate for hydrolase B than for hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of - and -naphthol and p-nitrophenol lowered the specific activities of the enzymes by about fivefold but improved stability under basic conditions. The optimum pH of mouse liver esterase with the acetate, methylcarbonate, and ethylthiocarbonate of -naphthol was between pH 7.0 and pH 7.6. Human and mouse liver microsomal esterase activities were about five orders of magnitude lower than the esterase activities of purified rat liver hydrolase B. A relationship between the catalytic activity of the enzymes and the lipophilicity of the naphthyl substrates indicated that (i) in the - and -naphthyl carbonate series, an inverse relationship between enzyme activity and lipophilicity of the substrates was observed, whereas (ii) in the -naphthyl carboxylate series, an increase in enzyme activity with increasing lipophilicity of the substrates up to a log P value of about 4.0 was observed, after which the enzyme activity decreased. 相似文献
67.
Shao Zezhi Li Yuping Krishnamoorthy Ramesh Chermak Todd Mitra Ashim K. 《Pharmaceutical research》1993,10(2):243-251
Various surfactants were investigated to compare their effects on insulin dissociation, -chymotryptic degradation, and rat enteral absorption. With a circular dichroism technique, sodium dodecyl sulfate (SDS) at a 5 mM concentration was found to completely dissociate procine-zinc insulin hexamers (0.5 mg/ml) into monomers. The catalytic activity of -chymotrypsin (0.5 µM) was also abolished by 5 mM SDS. When insulin was injected into the distal jejunum/ proximal ileum segment of the rat, 5 mM SDS greatly enhanced its pharmacological availability, from a negligible value to 2.8%. Being a cationic surfactant, hexadecyl trimethylammonium bromide (CTAB) also efficiently dissociated insulin hexamers at concentrations of 1–5 mM. However, extensive charge–charge interaction was observed below a CTAB concentration of 0.6 mM, leading to insulin precipitation at a molar CTAB:insulin ratio of 1:1 to 2:1. An -chymotryptic degradation study also revealed near-complete dissociation of insulin hexamers at 1 mM CTAB. Above 1 mM, however, CTAB acted as an enzyme inhibitor, most likely by means of charge repulsion. Enteral absorption studies showed a much lower pharmacological availability, only 0.29%. Nonionic surfactants such as Tween 80 and polyoxyethylene 9 lauryl ether were ineffective in dissociating insulin hexamers. Tween 80, at 5 mM, neither significantly altered the -chymotryptic degradation pattern nor enhanced the enteral absorption of insulin. The relative effectiveness of different species of bile salts on insulin hexamer dissociation appeared to be similar. Sodium glycocholate at a 30 mM concentration also significantly increased insulin pharmacological availability, to 2.3%. A morphological study did not reveal any significant alteration of the rat intestinal mucosal integrity after exposure to 5 mM SDS for 30 min. The results further emphasize the importance of the degree of insulin aggregation on its enteral transport. 相似文献
68.
Summary Rat brain cortex slices and synaptosomes preincubated with [3H]noradrenaline were used to investigate whether the NMDA-evoked noradrenaline release is modulated by agonists or antagonists at presynaptic 2-adrenoceptors.In experiments on slices, noradrenaline and the preferential 2-adrenoceptor agonists talipexole (former B-HT 920) and clonidine inhibited the NMDA evoked tritium overflow whereas the selective 1-adrenoceptor agonists cirazoline and methoxamine were ineffective. The 2-adrenoceptor antagonists rauwolscine and idazoxan facilitated the NMDA-evoked tritium overflow whereas the preferential 1-adrenoceptor antagonist prazosin was ineffective. The concentration-response curve of talipexole for its inhibitory effect on NMDA-evoked overflow was shifted to the right by idazoxan (apparent pA2 = 7.5). The EC50 of NMDA (97 mol/l) for its stimulating effect on tritium overflow was not substantially changed by blockade of 2-autoreceptors with 1 mol/l rauwolscine (EC50 of NMDA in the presence of the 2-adrenoceptor antagonist, 155 mol/l), but the maximal overflow of tritium was increased 2.5 fold by this rauwolscine concentration. In experiments on synaptosomes, talipexole and noradrenaline inhibited the NMDA-evoked tritium overflow. The inhibitory effect of talipexole was abolished by idazoxan which, given alone, was ineffective, as was prazosin. Talipexole did also not produce an inhibition when tritium overflow was evoked by NMDA in the presence of -conotoxin GVIA 0.1 mol/l; the latter, by itself, decreased the response to NMDA by about 55%. It is concluded that the NMDA-evoked noradrenaline release in the cerebral cortex is modulated via presynaptic 2-adrenoceptors on the noradrenergic neurones. Stimulation of these autoreceptors in slices by endogenous noradrenaline does not result in a decreased potency of NMDA, but in a decreased maximum effect, in stimulating noradrenaline release. The inhibitory effect of 2-adrenoceptor agonists on the NMDA-evoked release is at least partially due to a functional interaction between the NMDA receptors and 2-autoreceptors at the level of the same varicosities. The results obtained with -conotoxin GVIA suggest that Ca2+ influx via the N-type voltage-sensitive calcium channel (VSCC) occurs in response to NMDA receptor stimulation and contributes substantially to the induction of NMDA-evoked noradrenaline release. The inhibitory effect of 2-adrenoceptor stimulation on this release appears to be ultimately due to an inhibition of the influx of Ca2+ via the N-type VSCC.
Correspondence to: M. Göthert at the above address 相似文献
69.
Summary Guinea pig vas deferens was used as an animal model for alpha-1 adrenoceptor (1-receptor) mediated contractions in human hyperplastic prostatic tissue. The selective 1-receptor agonist, phenylephrine (PE), induced fully reversible, dose-dependent contractions antagonized by increasing concentrations of the 1-receptor blockers prazosin (1–100 nM) and YM 617 (0.1–10 nM). Removal of extracellular Ca2+ reduced PE-evoked contractions in a time-dependent manner. Nifedipine (1–1000 nM), a blocker of voltage-dependent L-type Ca2+ channels (VDCC), inhibited the PE-induced response by up to 65%. Removal of extracellular Ca2+ abolished the 1-agonist reactivity in a time-dependent fashion. To elucidate the participation of intracellular Ca2+ stores in 1-receptor contractions, the tissue was pretreated with ryanodine (10 M) or thapsigargin (0.1 M), established inhibitors of Ca2+ release from intracellular pools. Both substances reduced the PE contractions by up to 80%. Nifedipine suppressed the remaining contractions completely. This provides evidence that Ca2+ influx through VDCC and Ca2+ release from intracellular stores contribute to 1-receptor contractions in the guinea pig vas deferens and may be important in obstructive benign prostatic hyperplasia. 相似文献
70.
Kensuke Yamazumi Shigeharu Terukina Michio Matsuda Jun-ichi Kanbayashi Masato Sakon Toshimasa Tsujinaka 《Surgery today》1993,23(1):45-50
We discovered a congenital heterozygous dysfibrinogen in a patient and reported this case in relation to surgery some time ago (Jpn J Surg (1988) 18:43–46).3 Further studies on the isolated abnormal population of fibrinogen derived from this patient have revealed that fibrinopeptide A was not cleaved by ancrod, a snake venom-derived thrombin-like enzyme, but by thrombin, slowly but completely. The released fibrinopeptide A components, being the A, AY, and AP peptides, were all found to be abnormal, as evidenced by slightly earlier elution positions on high-performance liquid chromatography, compared with the normal counterparts. By analyzing their amino acid sequence, we have identified an arginine to histidine substitution at position 16 of the A chain, the thrombin cleavage site. Utilizing insolubilized abnormal fibrinogen, we confirmed that the polymerization site assigned to the central E domain, the A site, was exposed by thrombin, but not by ancrod. This dysfibrinogen, designated as fibrinogen Osaka IV, is the second abnormal molecule with an A arginine-16 to histidine substitution identified among Japanese families. 相似文献