全文获取类型
收费全文 | 2481篇 |
免费 | 190篇 |
国内免费 | 202篇 |
专业分类
2873篇 |
出版年
2024年 | 7篇 |
2023年 | 31篇 |
2022年 | 77篇 |
2021年 | 107篇 |
2020年 | 73篇 |
2019年 | 91篇 |
2018年 | 92篇 |
2017年 | 67篇 |
2016年 | 107篇 |
2015年 | 164篇 |
2014年 | 176篇 |
2013年 | 211篇 |
2012年 | 215篇 |
2011年 | 194篇 |
2010年 | 137篇 |
2009年 | 105篇 |
2008年 | 125篇 |
2007年 | 121篇 |
2006年 | 104篇 |
2005年 | 101篇 |
2004年 | 90篇 |
2003年 | 93篇 |
2002年 | 81篇 |
2001年 | 44篇 |
2000年 | 28篇 |
1999年 | 25篇 |
1998年 | 16篇 |
1997年 | 10篇 |
1996年 | 11篇 |
1995年 | 8篇 |
1994年 | 7篇 |
1992年 | 12篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 12篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 9篇 |
1985年 | 9篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1979年 | 5篇 |
1977年 | 10篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 6篇 |
1969年 | 4篇 |
排序方式: 共有2873条查询结果,搜索用时 13 毫秒
41.
Lui Ng Timothy Ming-Hun Wan Colin Siu-Chi Lam Ariel Ka-Man Chow Sunny Kit-Man Wong Johnny Hon-Wai Man Hung-Sing Li Nathan Shiu-Man Cheng Ryan Chung-Hei Pak Alvin Ho-Kwan Cheung Thomas Chung-Cheung Yau Oswens Siu-Hung Lo Dominic Chi-Chung Foo Jensen Tung-Chung Poon Ronnie Tung-Ping Poon Roberta Wen-Chi Pang Wai-Lun Law 《PloS one》2015,10(5)
BackgroundThe overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients.MethodsThis randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients. We determined plasma levels of OPN by ELISA and examined their correlation with the clinicopathological parameters of CRC patients. The effects of endogenous and exogenous OPN on CRC metastasis were investigated by examination of the effect on regulators of epithelial to messenchymal transition and migration assay.ResultsOur findings demonstrated for the first time the clinical correlation of plasma OPN with metastasis of CRC patients. High post-operative plasma OPN level (>153.02 ng/ml) associated with development of metastasis after curative resection (p<0.001). Moreover, post-operative plasma OPN level correlated with disease-free survival of CRC patients (p=0.009) and was an independent factor for predicting development of metastasis in CRC patients after curative resection (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1 cell migration through Snail and Twist1 overexpression and E-cadherin repression, and secretory OPN level enhanced cell migration.ConclusionsThe results of the current study suggest that post-operative plasma OPN correlated with post-operative metastasis, suggesting that it is a potential non-invasive biomarker for the development of future metastasis in CRC patients. In addition, OPN was shown to be involved in the metastatic process and thus inhibition of OPN is a potential therapeutic approach to treat CRC patients. 相似文献
42.
A common variant in the MTNR1b gene is associated with increased risk of impaired fasting glucose (IFG) in youth with obesity 下载免费PDF全文
43.
Regulation of K+ current in human airway epithelial cells by exogenous and autocrine adenosine 总被引:4,自引:0,他引:4
Szkotak Artur J.; Ng Amy M. L.; Sawicka Jolanta; Baldwin Stephen A.; Man S. F. Paul; Cass Carol E.; Young James D.; Duszyk Marek 《American journal of physiology. Cell physiology》2001,281(6):C1991
The regulatory actions ofadenosine on ion channel function are mediated by four distinctmembrane receptors. The concentration of adenosine in the vicinity ofthese receptors is controlled, in part, by inwardly directed nucleosidetransport. The purpose of this study was to characterize the effects ofadenosine on ion channels in A549 cells and the role of nucleosidetransporters in this regulation. Ion replacement and pharmacologicalstudies showed that adenosine and an inhibitor of human equilibrative nucleoside transporter (hENT)-1, nitrobenzylthioinosine, activated K+ channels, most likely Ca2+-dependentintermediate-conductance K+ (IK)channels. A1 but not A2 receptor antagonistsblocked the effects of adenosine. RT-PCR studies showed that A549 cellsexpressed mRNA for IK-1 channels as well asA1, A2A, and A2B but notA3 receptors. Similarly, mRNA for equilibrative (hENT1 andhENT2) but not concentrative (hCNT1, hCNT2, and hCNT3) nucleosidetransporters was detected, a result confirmed in functional uptakestudies. These studies showed that adenosine controls the function ofK+ channels in A549 cells and that hENTs play a crucialrole in this process. 相似文献
44.
我国两株登革2型病毒5′和3′端非编码区序列测定及二级结构分析 总被引:1,自引:0,他引:1
为测定我国两株临床症状、乳鼠神经毒力不同的登革 2型病毒流行株 5′和 3′端非编码区序列 (untranslated region,UTR) ,分析二级结构差异与毒力变化的关系 ,分别从 D2 - 0 4、D2 - 44株感染的 C6/ 36细胞及鼠脑中提取总 RNA.以该 RNA为模板 ,利用 RACE法 ,分别扩增了 D2 - 0 4、D2 -44株的 5′和 3′末端 c DNA片段 .将其分别与 p GEM- T载体连接得到重组质粒 ,测定上述 c DNA插入片段的序列 .用 RNAdraw软件预测 D2 - 0 4、D2 - 44株 5′和 3′端非编码区的二级结构 .D2 - 0 4、D2 -44株 5′端和 3′端非编码区分别有 96和 454个核苷酸 .其中 5′非编码区 59位 C(D2 - 0 4 )→T(D2 -44 ) ,使 D2 - 44二级结构稳定性下降 ;3′端非编码区有 1 5个核苷酸不同 ,其中 T(355)→ A,T(32 6)→ G引起了所在位置二级结构自由能变化 ,且分别位于两个保守序列区 (conserved sequence,CS)CS1、CS2 A.这些位点变化可能与毒力有关 . 相似文献
45.
Monitoring and classification of PAH toxicity using an immobilized bioluminescent bacteria 总被引:6,自引:0,他引:6
An immobilized recombinant bioluminescent Escherichia coli strain, harboring a lac::luxCDABE fused plasmid, which shows lower bioluminescence levels when cellular metabolism is inhibited, was used to monitor the cellular toxicity of polycyclic aromatic hydrocarbons (PAHs). PAHs, classified as pericondensed (PCPAHs) or catacondensed (CCPAHs) according to their molecular structures, were differentiable according to the response of this biosensor. Only CCPAHs were found to cause cellular toxicity, resulting in a dose-dependent decrease in the bioluminescent output. The induction of cellular toxicity by CCPAHs and PCPAHs was compared with acute toxicity predictions obtained using the quantitative structure-activity relationship (QSAR) model. A good relationship was obtained between the toxicities determined with the bioluminescent response of the immobilized bacterium GC2 and the QSAR model. It was also found that the present study offers a new method of predicting the cellular toxicities of CCPAHs or PCPAHs using this biosensor. 相似文献
46.
Yu Pang Qiang Li Xichao Ou Hojoon Sohn Zhiying Zhang Junchen Li Hui Xia Kai Man Kam Richard J. O’Brien Junying Chi Shitong Huan Daniel P. Chin Yan-lin Zhao 《PloS one》2013,8(7)
Background
Genechip (CapitalBio, Beijing, China) is a system for diagnosing resistance to rifampin and isoniazid, which shows high efficiency in detecting drug-resistant tuberculosis. Here, we firstly evaluated the costs of Genechip for detecting the drug susceptibility of Mycobacterium tuberculosis, compared to conventional drug susceptibility test (DST) in laboratories in China.Methodology/Principal Findings
Data on the costs of the two tests were collected at four hospitals. Costs were calculated using the essential factor cost calculation method. The costs of diagnosing a single case of multidrug-resistant tuberculosis (MDR-TB) using Genechip and DST were US$22.38 and $53.03, respectively. Taking into account the effect on costs from failure of a certain number of tests to accurately diagnose MDR-TB, the costs of Genechip and DST increased by 17.65% and 5.22%, respectively. The cost of both tests decreased with the increasing prevalence of MDR-TB disease, and the cost of Genechip at a sensitivity of more than 50% was lower than that of DST. When price of Genechip was varied to 50%, 80%, 150%, and 200% of the original price, the cost of Genechip at sensitivities of more than 30%, 40%, 60%, and 70%, respectively, was also lower than that of DST.Conclusions/Significance
This study showed that Genechip was a more cost-effective method of diagnosing MDR-TB compared to conventional DST. 相似文献47.
Pan Wu Man Wang Ting Zhang Xiaxiu Tong Taihe Xiang 《Plant Cell, Tissue and Organ Culture》2018,132(3):433-447
The influence of light quality and cytokinin content in media on growth, development, photosynthetic pigments and secondary metabolite content of Myrtus communis L. was evaluated in an in vitro culture. Various treatments with light emitting diodes (LEDs): 100% blue (B), a mix of 70% red and 30% blue (RB) and 100% red were applied and compared with a traditional fluorescent lamp as control. Axillary shoots were incubated on Murashige and Skoog medium with 30 g dm?3 sucrose, 0.5% BioAgar, 0.5 μM 1-naphthaleneacetic acid and different concentrations of 6-benzyladenine (BA): 1, 2.5 and 5 µM. Cultures were maintained for 6 weeks in 23/21?±?1 °C (day/night), 80% relative humidity and 16/8 h photoperiod; photosynthetic photon flux density (PPFD) was 35 µmol m?2 s?1 in all treatments. Light spectra and BA content in media affected biometrical and phytochemical M. communis properties. Red LEDs and 5 µM BA resulted in the highest multiplication rate. The highest shoots were obtained under red LEDs, but with the lowest concentration of cytokinin in media. Fresh weight was greatest on LEDs containing blue light in the spectrum (B and RB); moreover, 5 µM BA increased dry weight. Photosynthetic pigment levels were lower under LED light compared to control lamps. Phenolic acids and flavonoids were identified in M. communis leaf extracts. Myricetin was the major constituent with highest concentration under red LEDs and highest BA level. 相似文献
48.
表达SLTEC保护性抗原的重组猪霍乱沙门氏菌C500株的构建及生物学特性 总被引:1,自引:0,他引:1
摘要:【目的】 利用平衡致死系统构建表达产类志贺氏毒素大肠杆菌(Shiga-like toxin Escherichia coli , SLTEC)保护性抗原的减毒猪霍乱沙门氏菌。【方法】 构建表达SLT-IIeB-FedF的重组质粒 ,再将其电转入终宿主菌减毒猪霍乱沙门氏菌ΔasdC500株中构建成口服活疫苗株 ,经聚丙烯酰胺凝胶电泳检测SLT-IIeB-FedF融合蛋白的表达情况,并观察重组菌体外培养的稳定性。【结果】 利用宿主-载体平衡致死系统构建了表达SLTEC保护性抗原的重组减毒猪霍乱沙门氏菌 相似文献
49.
Man Il Kim Jee Yeon Baek Min Jee Kim Heon Cheon Jeong Ki-Gyoung Kim Chang Hwan Bae Yeon Soo Han Byung Rae Jin Iksoo Kim 《Molecules and cells》2009,28(4):347-363
The 15,389-bp long complete mitogenome of the endangered red-spotted apollo butterfly, Parnassius bremeri (Lepidoptera: Papilionidae) was determined in this study. The start codon for the COI gene in insects has been extensively discussed, and has long remained a matter of some controversy. Herein, we propose that the CGA (arginine) sequence functions as the start codon for the COI gene in lepidopteran insects, on the basis of complete mitogenome sequences of lepidopteran insects, including P. bremeri, as well as additional sequences of the COI start region from a diverse taxonomic range of lepidopteran species (a total of 53 species from 15 families). In our extensive search for a tRNA-like structure in the A+T-rich region, one tRNATrp-like sequence and one tRNALeu (UUR)-like sequence were detected in the P. bremeri A+T-rich region, and one or more tRNA-like structures were detected in the A+T-rich region of the majority of other sequenced lepidopteran insects, thereby indicating that such features occur frequently in the lepidopteran mitogenomes. Phylogenetic analysis using the concatenated 13 amino acid sequences and nucleotide sequences of PCGs of the four macrolepidopteran superfamilies together with the Tortricoidea and Pyraloidea resulted in the successful recovery of a monophyly of Papilionoidea and a monophyly of Bombycoidea. However, the Geometroidea were unexpectedly identified as a sister group of the Bombycoidea, rather than the Papilionoidea. 相似文献
50.
血管内皮生长因子基因对兔髂动脉内膜损伤的组织形态变化过程的影响 总被引:1,自引:0,他引:1
探讨血管内皮细胞的特异丝裂原-血管内皮生长因子(VEGF)基因阻止血管内膜损伤后形成再狭窄的组织变化过程。建立球囊拉伤血管内膜的兔髂动脉模型,将携带VEGF目的基因的真核表达载体pcDNA3/VEGF经多聚赖氨酸处理的PTCA球囊导管导入拉伤的血管内膜。VEGF基因组拉伤2周时血管内壁有VEGF mRNA和蛋白的高表达。血管内膜内皮化较快。2周时即有许多血管内皮细胞呈岛状分布。4周时内膜基本恢复光滑。内膜平滑肌细胞增生明显减少,而对照组2周时血管内膜粗糙,基底膜暴露,拉伤后4周仍无内皮细胞再生,最后形成虫蚀样改变。血管中膜平滑肌细胞穿过内弹性膜进入内膜并大量增生,内膜增厚。VEGF基因定位导入血管内壁后。VEGF mRNA和蛋白高表达且发挥其生物学效应,内皮细胞岛状增生,加快内膜内皮化,减轻内膜增厚。 相似文献