全文获取类型
收费全文 | 594篇 |
免费 | 24篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 2篇 |
妇产科学 | 9篇 |
基础医学 | 146篇 |
口腔科学 | 8篇 |
临床医学 | 40篇 |
内科学 | 75篇 |
皮肤病学 | 8篇 |
神经病学 | 60篇 |
特种医学 | 42篇 |
外科学 | 21篇 |
综合类 | 46篇 |
预防医学 | 39篇 |
眼科学 | 2篇 |
药学 | 109篇 |
中国医学 | 9篇 |
肿瘤学 | 15篇 |
出版年
2022年 | 14篇 |
2021年 | 13篇 |
2020年 | 6篇 |
2019年 | 4篇 |
2018年 | 4篇 |
2017年 | 6篇 |
2016年 | 12篇 |
2015年 | 18篇 |
2014年 | 21篇 |
2013年 | 36篇 |
2012年 | 21篇 |
2011年 | 40篇 |
2010年 | 24篇 |
2009年 | 26篇 |
2008年 | 32篇 |
2007年 | 23篇 |
2006年 | 31篇 |
2005年 | 27篇 |
2004年 | 30篇 |
2003年 | 22篇 |
2002年 | 18篇 |
2001年 | 19篇 |
2000年 | 15篇 |
1999年 | 12篇 |
1998年 | 15篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 16篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 10篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 10篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1971年 | 2篇 |
排序方式: 共有631条查询结果,搜索用时 15 毫秒
41.
John B Ochola Wilber Lwande Thuku Thiong'o Lucie Rogo Rafael Herrmann Eric Schepers Richard Bagine Paul Mungai Isaiah O Ndiege 《Toxicon》2007,50(4):449-456
Venoms were collected from two scorpion species: Parabuthus leiosoma and Parabuthus pallidus from Kenya. Subcutaneous injection and oral toxicity tests of crude and pure fractions of scorpion venoms were done in Mus musculus (mice), Chilo partellus and Busseola fusca. The highest activity against C. partellus was found in P. leiosoma venom (LC(50) 0.689 mg/50mg body weight). Bioassay-guided purification by a combination of cation-exchange (CE) and reverse-phase high-performance liquid chromatography (RP-HPLC) led to the isolation of three toxic peptides. A lepidopteran-selective toxin (P. leiosoma insect toxin, Plit) was isolated, and the partial N-terminal amino acid sequence (-KDGYPVDNANCKYE-) plus the molecular weight (6688.5 Da) determined. A peptide with significant insect toxicity coupled with mild effects on mice (P. leiosoma toxin, Plt) was isolated, and the partial N-terminal amino acid sequence (-LCEKFKVQRLVELNCVD-) plus the molecular weight (6742.5 Da) was determined. Another toxin with anti-mammalian activity (P. leisoma mammal-selective toxin, Plmt), and N-terminal partial amino acid sequence of ADVPGNYPLDKNGNRYY- plus a molecular weight of 7145.5 Da was also isolated. Comparison of the partial N-terminal amino acid sequences with other toxins revealed that Plit shows high homology to other known insect toxins. Similarly, Plmt shows high homology with several birtoxin-like anti-mammalian toxins. Plt does not exhibit homology with any known scorpion toxin with combined anti-insect and anti-mammalian activity. 相似文献
42.
In the search of new prodrugs effective against herpes simplex virus series of thymidine, 5-bromo-2′-deoxyuridine esters with amino acid and peptide chains and 3′-azido-2′,3′-dideoxythymidine derivatives have been synthesized and evaluated for antiviral activity. The chemical stability of some of them containing different residues was studied at pH 1 and 7.4 and temperature of 37°C. An HPLC method was developed for quantification of the unchanged ester concentration. It was proved that esters with simple aliphatic straight side chain (containing alanyl-, glycyl-, or glycyl-glycyl-glycyl-residues) are relatively stable both at acidic and neutral media, 37°C. Some of them undergo negligible hydrolysis with half lifes ranging between 6 and 23 h. In contrast, more complex esters with branched side chain (valyl-), with phenyl residue (phenylalanyl-), as well as containing thiazol ring are rather unstable especially at acidic conditions and undergo rapid hydrolysis resulting in the respective chemical precursor. The stability of the former group esters outlines them as suitable candidates for prodrugs: with higher lipophilicity facilitating po absorption, satisfying chemical stability and possibility to release the active moiety following enzymatic hydrolysis. 相似文献
43.
Application of footshock during the acquisition trial of a one-trial passive avoidance test is associated with a rise in the concentration of serotonin in the hippocampi of rats 24 hr after termination of the acquisition trial. Rats subjected to amnesic treatment with carbon dioxide (CO2) immediately after footshock do not show this rise in the hippocampal concentration of serotonin. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 (7D-Phe), alleviate CO2-induced amnesia for the passive avoidance response when administered 1 hr before retrieval test 24 hr after acquisition. These peptides do not have anti-amnesic activity when given before acquistion. Another ACTH-analogue, ACTH 11-24 does not affect amnesia, given before either the acquisition or the retrieval test. The anti-amnesic effect of ACTH 4-10 AND ACTH 4-10 (7D-Phe), was correlated with a rise in the hippocampal serotonin concentration similar to that observed in non-amnesic animals. Pre-acquisition treatment with ACTH 4-10 or administration of ACTH 11-24 did not affect hippocampal serotonin concentrations. Changes in the hippocampal concentrations of noradrenaline, dopamine, tryptophan and tyrosine were not related to the behavioural activity of any of the peptides. It is suggested that alterations in hippocampal serotonin metabolism 24 hr after acquisition of a passive avoidance response are associated with the retrieveability of the passive avoidance response. 相似文献
44.
Rats were given four daily, interperitoneal injections (80 micrograms/kg) of Met-enkephalin, (D-Ala2)-Met-enkephalin-NH2, beta-endorphin, (D-Ala2)-beta-endorphin or the diluent (0.9% NaCl acidified to, 0.01 M with acetic acid). Animals were subsequently tested for food and water inake and activity. Met-enkephalin injections did not affect any of the measures but its (D-Ala2) analog reduced food intake and some of the activity measures in a complicated way. beta-Endorphin injections did not affect food or water intake; in familiar situations these animals were less active while novel situations seemed to potentiate activity. The (D-Ala2) analog reduced wheel running over 24 hours. 相似文献
45.
Windisch M Hutter-Paier B Grygar E Doppler E Moessler H 《Journal of neural transmission (Vienna, Austria : 1996)》2005,112(10):1331-1343
Summary. The neuroprotective potency of N-PEP-12, a novel, proprietary compound consisting of biopeptides and amino acids was investigated.
Lesion models have been applied in neuronal cultures of embryonic chicken cortex, pre-treated with N-PEP-12 from the first
day onwards. On day 8 in vitro neurons were lesioned and cell viability was measured 24 and 48 hours later. To simulate acute
brain ischemia, cytotoxic hypoxia was induced by sodium cyanide or by iodoacetate and excitotoxicity by L-glutamate. Ionomycin
for up to 48 hours induced calcium overload. The cytoskeleton was disrupted by addition of colchicine. N-PEP-12 shows dose-dependent
neuroprotection in all different models. The effect size depends on the recovery time but also on the extent of the lesion.
In cases of mild to moderate lesion pronounced dose-dependent effects could be demonstrated. This indicates that chronic exposure
to N-PEP-12 is able to prevent neuronal cell death associated to conditions occurring during normal aging and neurological
disorders like ischemic stroke, hypoxia, brain trauma, or AD. 相似文献
46.
肾上腺髓质素及其受体在增生性玻璃体视网膜病变前膜中的表达 总被引:1,自引:1,他引:0
目的 探讨肾上腺髓质素(ADM)及其受体(ADMR)在增生性玻璃体视网膜病变(PVR)前膜中的表达。方法 标本取自2001年7-11月在我院眼科研究所确诊为孔源性视网膜脱离合并PVR行玻璃体手术的10例连续病例,PVR均为C级以上,采用原位杂交法对术中所取标本的ADM和ADMR mRNA表达情况进行观察。结果10例增生性玻璃体视网膜病变前膜中有7例ADM和ADMR mRNA阳性。阳性细胞内分布不均匀,部分细胞以胞质阳性为主,部分细胞的阳性主要出现在胞核。结论 ADM和ADMR在PVR前膜中表达,PVR的发病过程中有ADM和ADMR的参与。(中华眼科杂志,2004,4D:317-320) 相似文献
47.
Micro-HPLC and standard-size HPLC for the separation of peptide stereoisomers employing an ion-exchange principle 总被引:1,自引:0,他引:1
Czerwenka C Lämmerhofer M Lindner W 《Journal of pharmaceutical and biomedical analysis》2003,30(6):1789-1800
Standard-size (4 mm ID) and micro-HPLC columns (0.5 mm ID) packed with a quinine-based ion-exchange type chiral stationary phase are comparatively evaluated for the separation of peptide enantiomers with up to six amino acid residues. The results show that downscaling the separation system in order to gain the advantages of miniaturized HPLC is possible without sacrificing separation power. Further, five different N-terminal protections (3,5-dinitrobenzoyl, 2,4-dinitrophenyl, 3,5-dinitrobenzyloxycarbonyl, carbazole-9-carbonyl, and 9-fluorenylmethoxycarbonyl) of the analytes are investigated regarding their effect on enantioselectivity. A comparison between a hydro-organic and a polar-organic mobile phase is also reported. The enantiomers of the peptides containing one to four amino acid residues were baseline resolved, while for the penta- and hexamers only partial separations were possible. In addition, all four stereoisomers of alanylalanine could be baseline separated. 相似文献
48.
抗菌肽Alloferon-1串联式重组表达及其表达产物体外抗肿瘤活性的研究 总被引:1,自引:0,他引:1
目的:构建串联式表达Alloferon-1的原核重组表达系统,检测合成及重组表达的Alloferon-1体外抗肿瘤细胞活性。方法:采用连接引物PCR法,构建含6×His-EK-8×Alloferon-1-EK-6×His序列的人工融合基因;采用常规分子生物学方法克隆并构建该人工融合基因及其原核表达系统;采用SDS-PAGE和BioRad凝胶图象分析系统了解目的重组产物8×rAlloferon-1-EK表达情况和产量;采用Ni-NTA亲和层析及EK酶切和Sephadex G-50层析法提纯8×rAlloferon-1-EK及rAlloferon-1-EK;采用MTT法检测rAlloferon-1-EK体外抑制KB、SGC和HL-60肿瘤细胞增殖的作用,并与直接合成的Alloferon-1(sAlloferon-1)和Alloferon-1-EK(sAlloferon-1-EK)的抗肿瘤作用比较。结果:获得了序列正确的目的人工融合基因克隆及其原核表达系统pET42a-8×rAlloferon-1-EK-E.coliBLDE3。在IPTG诱导下,该原核重组表达系统可表达串联式目的重组蛋白8×rAlloferon-1-EK,其产量约为细菌总蛋白的30%。Ni-NTA和Sephadex G-50层析后,可分别获得8×rAlloferon-1-EK和rAlloferon-1-EK。在25~100μg/ml剂量范围内,sAlloferon-1、sAlloferon-1-EK和rAlloferon-1、rAlloferon-1-EK均有明显抑制KB、SGC和HL-60肿瘤细胞生长及增殖的效果(P<0.01),且四者抑制作用无明显差异(P>0.05)。结论:本研究成功构建了串联表达rAlloferon-1的原核表达系统,其表达产物具有与合成的Alloferon-1和Alloferon-1-EK相似的体外抗肿瘤细胞活性。 相似文献
49.
目的研究改造后的血管生成抑制相关肽(21肽)抗血管生成活性及对人宫颈癌Hela细胞皮下移植裸鼠模型的抑制作用,探讨其抑瘤作用机制。方法2005年8月至2006年2月哈尔滨医科大学第一临床医学院进行Hela细胞株皮下接种裸鼠造模,21肽治疗3周后,处死动物剥离肿瘤,称重并计算抑瘤率。免疫组化方法检测21肽对肿瘤组织的微血管密度(MVD)、增殖细胞核抗原(PCNA)和血管内皮生长因子(VEGF)的影响。结果21肽组平均抑瘤率可达51.89%,肿瘤组织微血管密度明显降低,与对照组比较差异有统计学意义(P〈0.05);21肽组肿瘤组织的PCNA、VEGF呈低表达,与对照组比较差异有统计学意义(P〈0.05)。结论21肽具有显著的抗血管生成活性,可明显地抑制裸鼠宫颈癌细胞的生长,其抑制宫颈癌的作用机制可能与其降低新生血管形成和调解血管生成相关因子的表达有关。 相似文献
50.
肽类生长因子对神经系统发育发挥着重要的调控作用,与神经退行性疾病的发生和发展也密切相关,在研究过程中要运用哲学原理作指导,充分认识肽类生长因子结构和功能的多样性、其受体及其作用机制的复杂性,处理好基础研究与实践的辨证关系,从单纯分析研究走向系统研究。 相似文献