全文获取类型
收费全文 | 18480篇 |
免费 | 897篇 |
国内免费 | 564篇 |
出版年
2023年 | 289篇 |
2022年 | 439篇 |
2021年 | 521篇 |
2020年 | 562篇 |
2019年 | 735篇 |
2018年 | 589篇 |
2017年 | 378篇 |
2016年 | 380篇 |
2015年 | 458篇 |
2014年 | 986篇 |
2013年 | 1307篇 |
2012年 | 723篇 |
2011年 | 1047篇 |
2010年 | 707篇 |
2009年 | 822篇 |
2008年 | 879篇 |
2007年 | 912篇 |
2006年 | 767篇 |
2005年 | 675篇 |
2004年 | 604篇 |
2003年 | 487篇 |
2002年 | 402篇 |
2001年 | 294篇 |
2000年 | 221篇 |
1999年 | 248篇 |
1998年 | 257篇 |
1997年 | 204篇 |
1996年 | 225篇 |
1995年 | 178篇 |
1994年 | 169篇 |
1993年 | 147篇 |
1992年 | 155篇 |
1991年 | 130篇 |
1990年 | 120篇 |
1989年 | 110篇 |
1988年 | 114篇 |
1987年 | 118篇 |
1986年 | 111篇 |
1985年 | 195篇 |
1984年 | 284篇 |
1983年 | 231篇 |
1982年 | 255篇 |
1981年 | 208篇 |
1980年 | 224篇 |
1979年 | 218篇 |
1978年 | 179篇 |
1977年 | 140篇 |
1976年 | 123篇 |
1975年 | 112篇 |
1974年 | 112篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
911.
Jonathan M. Rawson Richard H. Heineman Lauren B. Beach Jessica L. Martin Erica K. Schnettler Michael J. Dapp Steven E. Patterson Louis M. Mansky 《Bioorganic & medicinal chemistry》2013,21(22):7222-7228
The nucleoside analog 5,6-dihydro-5-aza-2′-deoxycytidine (KP-1212) has been investigated as a first-in-class lethal mutagen of human immunodeficiency virus type-1 (HIV-1). Since a prodrug monotherapy did not reduce viral loads in Phase II clinical trials, we tested if ribonucleotide reductase inhibitors (RNRIs) combined with KP-1212 would improve antiviral activity. KP-1212 potentiated the activity of gemcitabine and resveratrol and simultaneously increased the viral mutant frequency. G-to-C mutations predominated with the KP-1212-resveratrol combination. These observations represent the first demonstration of a mild anti-HIV-1 mutagen potentiating the antiretroviral activity of RNRIs and encourage the clinical translation of enhanced viral mutagenesis in treating HIV-1 infection. 相似文献
912.
913.
Naeimeh Safavizadeh Seyed Ali Rahmani Mohamad Zaefizadeh 《Indian journal of human genetics》2013,19(1):18-25
INTRODUCTION:
Multiple sclerosis (MS) is an autoimmune inflamatory disease, which affects the (Central Nervous System) and leads to the destruction of myelin and atrophy of the axons. Genetic factors, in addition to environmental ones, seem to play a role in MS. Numerous studies have reported mitochondrial defects including a reduction in cytochrome c oxidase (COX) complex function related to the reduction of mitochondrial genes expression in the cortex tissue of patients with MS have been reported.MATERIALS AND METHODS:
This study aimed to assess COX5B and COX2 genes expression in MS patients and compare it with normal subjects. We determine expression levels of genes COX5B and COX2, and also gene reference ß-actine using real–time polymerase chain reaction (RT-PCR) method. Data were obtained and obtained and standardized with the gene reference and were analyzed using independent sample t-test with SPSS and Excel programs.RESULT AND DISCUSSION:
The resultshowed COX5B gene expression reduced significant in MS patients compared to normal subjects (P < −0.05) whereas, there was no significant difference in the COX2 gene expression between normal subjects and patients. Thus, it can be claimed that down-regulation of mitochondrial electron transport chain genes supported the hypothesis that hypoxia-like tissue injury in MS may be due to mitochondrial genes, different expression impairment. 相似文献914.
5-氨基乙酰丙酸 (ALA) 是生物体内四吡咯类化合物的合成前体,在农业及医药领域应用广泛,是极具开发价值的高附加值生物基化学品。目前利用外源C4途径的重组大肠杆菌发酵生产ALA的研究主要利用LB培养基并添加葡萄糖和琥珀酸、甘氨酸等合成前体,成本较高。琥珀酸在C4途径中以琥珀酰辅酶A的形式直接参与ALA的合成。文中在以葡萄糖为主要碳源的无机盐培养基中研究了琥珀酰辅酶A下游代谢途径琥珀酸脱氢酶编码基因sdhAB和琥珀酰辅酶A合成酶编码基因sucCD缺失对ALA积累的影响。与仅表达异源ALA合成酶的对照菌株相比,sdhAB和sucCD缺失菌株ALA的产量分别提高了25.59%和12.40%,且ALA的积累不依赖于琥珀酸的添加和LB培养基的使用,从而大幅降低了生产成本,显示出良好的工业应用前景。 相似文献
915.
对高致病性禽流感病毒感染最为有效的治疗应采用抗病毒和抗炎症的联合治疗.本试验用流感病毒H5N1感染不同细胞株(A549细胞和MDCK细胞),采用不同浓度格尔德霉素对病毒感染细胞培养物作用不同时长,检测流感病毒滴度;ELISA检测格尔德霉素作用于流感病毒H5N1感染A549细胞12 h、24 h促炎性细胞因子IFN-α、TNF-α和IL-6水平.结果显示,流感病毒H5N1感染A549细胞和MDCK细胞,格尔德霉素极显著地抑制了流感病毒H5N1在细胞培养物的增殖(P < 0.01),而在病毒感染36 h和48 h,格尔德霉素并没有显著抑制流感病毒在MDCK细胞上的增殖(P > 0.05).促炎性细胞因子分析结果显示,格尔德霉素在流感病毒感染A549细胞12 h和24 h均显著降低了促炎性细胞因子IFN-α、TNF-α和IL-6的分泌(P < 0.05).上述实验结果显示,格尔德霉素具有抑制流感病毒H5N1增殖及其所介导的炎性反应的双重效应,为格尔德霉素成为应对流感病毒流行的备选药物提供基础科学依据. 相似文献
916.
为了研究元宝草(Hypericum sampsonii Hance)全草的化学成分,利用硅胶柱层析、Sephadex LH-20等色谱技术对元宝草三氯甲烷部位进行分离和纯化,共得到6个化合物,通过1H NMR、13C NMR、HMQC、HMBC等波谱技术分别鉴定为2,6-二羟基-4,3’,5’-三甲氧基二苯甲酮(1)、1,3,6-三羟基-2-甲基蒽醌(2)、山奈酚(3)、木犀草素(4)、3,4-二羟基苯甲酸乙酯(5)、β-谷甾醇(6),其中化合物1为新化合物,化合物2和5首次从该植物中分离得到。 相似文献
917.
目的研究G蛋白偶联受体(G protein-coupled receptors)激酶5(GPCR kinase-5,GRK5)基因缺陷和老化交互作用对阿尔茨海默病(Alzheimer's disease,AD)早期的病理改变-海马内肿胀轴突丛(swollen axonal clusters,SACs)出现和积累的影响。方法选取5、6、7、9、12~13、18—19月龄雌性GRK5基因敲除小鼠(GRK5 Knockout,GRK5KO)作为观察对象,另选取年龄匹配的雌性野生型(wild type,WT)小鼠为对照,每个年龄段GRK5KO和WT小鼠各4只。用抗人神经原纤维缠结(neurofibrillary tangles,NFTs)特异性抗体的免疫荧光染色方法观察海马内SACs的变化。结果所有小鼠随着年龄增长,海马内SACs逐渐增加;GRKSKO小鼠组海马内NFT^+ SACs数量较WT型小鼠组显著增加(P〈0.01);双因素方差分析显示遗传性GRK5基因缺陷和老化双因素对海马内NFT^+SACs的影响有显著协同效应(P〈0.01)。结论在促进早期AD病理发生的过程中,GRK5缺陷和老化双因素共同加剧了雌性GRKSKO小鼠海马内SACs的形成与积累。 相似文献
918.
《Phytomedicine》2013,21(14):1272-1279
This study aimed to investigate the effect of magnolol (5,5′-diallyl-2,2′-biphenyldiol) on contraction in distal colonic segments of rats and the underlying mechanisms. Colonic segments were mounted in organ baths for isometric force measurement. Whole-cell voltage-sensitive L-type Ca2+ currents were recorded on isolated single colonic smooth muscle cells using patch-clamp technique. The spontaneous contractions and acetylcholine (ACh)- and Bay K 8644-induced contractions were inhibited by magnolol (3–100 μM). In the presence of Bay K8644 (100 nM), magnolol (10–100 μM) inhibited the contraction induced by 10 μM ACh. By contrast, tetrodotoxin (100 nM) and Nώ-nitro-l-arginine methyl ester (l-NAME 100 μM) did not change the inhibitory effect of magnolol (10 μM). In addition, magnolol (3–100 μM) inhibited the L-type Ca2+ currents. The present results suggest that magnolol inhibits colonic smooth muscle contraction through downregulating L-type Ca2+ channel activity. 相似文献
919.
The trypsin inhibitors in buckwheat seeds were isolated by affinity chromatography on trypsin-Sepharose 4B, and the components were fractionated by chromatography on DEAE-Sepharose CL-6B. The major components, inhibitors I, II and III, were found to be homogeneous proteins with molecular weight of about 8,000. Trypsin inhibitory activity was more pronounced than the chymotrypsin inhibitory activity in all the inhibitor preparation obtained. The three major inhibitors had similar amino acid compositions and had no detectable amounts of tryptophan and carbohydrate. A high level of acidic and basic amino acid residues and a low level of methionine, tyrosine and phenylalanine residues characterized the inhibitors. Although the inhibitors I and II were particularly thermostable, inhibitor III, the most abundant component, was shown to be relatively heat-labile. 相似文献
920.
Ichiro Tomida Hiroshi Kayahara Ryozo Iriye 《Bioscience, biotechnology, and biochemistry》2013,77(11):2549-2555
The degree of racemization in the several activated ester methods of the peptide synthesis was measured in using the critical racemization test, Pro-Val+Pro, with help of gas chromatography. The results were compared with that in the coupling reaction, Leu-Phe+Val, in which no racemization had been reported in the corresponding reaction conditions by F. Weygand et al., when the activated dipeptide esters had been prepared from Z-Leu+Phe-activated esters. The significantly higher racemization was observed in the methods of N-hydroxypiperidine ester and thiophenyl ester, even when the activated dipeptide esters were prepared from Z-Pro+Val-activated esters. On the other hand, almost no racemization was observed in the N-hydroxysuccinimide ester and p-nitrophenyl ester methods. A great extent of the racemization was detected when the activated dipeptide esters were prepared directly from Z-Pro-Val-OH. 相似文献