全文获取类型
收费全文 | 2715篇 |
免费 | 282篇 |
国内免费 | 1090篇 |
出版年
2024年 | 22篇 |
2023年 | 105篇 |
2022年 | 109篇 |
2021年 | 156篇 |
2020年 | 146篇 |
2019年 | 174篇 |
2018年 | 125篇 |
2017年 | 111篇 |
2016年 | 110篇 |
2015年 | 194篇 |
2014年 | 266篇 |
2013年 | 203篇 |
2012年 | 251篇 |
2011年 | 235篇 |
2010年 | 240篇 |
2009年 | 202篇 |
2008年 | 204篇 |
2007年 | 193篇 |
2006年 | 184篇 |
2005年 | 146篇 |
2004年 | 132篇 |
2003年 | 97篇 |
2002年 | 85篇 |
2001年 | 72篇 |
2000年 | 77篇 |
1999年 | 52篇 |
1998年 | 29篇 |
1997年 | 17篇 |
1996年 | 15篇 |
1995年 | 11篇 |
1994年 | 16篇 |
1993年 | 9篇 |
1992年 | 14篇 |
1991年 | 7篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 14篇 |
1987年 | 7篇 |
1986年 | 9篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1957年 | 1篇 |
1953年 | 1篇 |
1950年 | 2篇 |
排序方式: 共有4087条查询结果,搜索用时 31 毫秒
61.
目的:研究WntSa对Wnt3a处理过的melan—a细胞分泌黑色素的影响。方法:体外培养黑色素细胞(melan-a细胞),分别进行GFP、Wnt3a、Wnt3a+WntSa处理,比较细胞的突起,酪氨酸酶的活性以及黑素合成相关基因(TYR、TRP2、MITF)表达情况。结果:Wnt3a促进黑色素细胞突起的生长和TYR、TRP2、MITF的表达,而Wnt5a逆转了Wnt3a对黑色素细胞的作用。结论:Wnt5a抑制Wnt3a促黑素细胞黑素生成的作用,表明在melan.a黑素细胞中Wnt5a可有效抑制wnt经典通路。 相似文献
62.
目的:探究类风湿性关节炎伴间质性肺病中肿瘤标志物对肺功能的影响。方法:选取2011年3月至2013年3月我院收治的类风湿性关节炎患者88例,根据其是否伴有ILD,分为RA组53例和RA-ILD组35例。检测两组肺功能指标用力肺活量(FVC)、1s用力呼气容积(FEV1)、最大通气量百分比(MVV)、一氧化碳弥散量(DLCO),肿瘤标志物癌胚抗原CEA、癌抗原125(CA125)、癌抗原199(CA199)及抗环胍氨酸肽抗体(抗CCP抗体)的值,并利用统计学方法分析肿瘤标记物与肺功能指标、抗CCP抗体的相关性。结果:RA.ILD组FVC、FEV1、MVV、DLCO均比RA组低,CEA、CA125、CA199均比RA组高,结果比较差异显著具有统计学意义(P〈0.05)。但两组抗CCP抗体含量相比却无明显差异,不具有统计学意义(P〉0.05)。相关性分析显示,CEA与FVC、FEV1、MVV、DLCO呈负相关(P〈0.05),而CA125、CA199却与肺功能指标无相关性,CEA、CA125、CA199与抗CCP抗体均无相关性(P〉0.05)。结论:RA-ILD的肺功能指标均有明显下降,而肿瘤标志物表达水平却明显增高,CEA对肺功能损害影响较大,却与关节损害的关系不大,这为临床对类风湿性关节炎伴间质性肺病早诊断、早治疗提供了依据。 相似文献
63.
64.
65.
66.
Hongbo Zhao Zhiyong Ji Deji Tang Cong Yan Wenyang Zhao Cheng Gao 《Molecular biology reports》2013,40(2):819-827
Early brain injury (EBI) occurred after aneurismal subarachnoid hemorrhage (SAH) strongly determined the patients’ prognosis. Autophagy was activated in neurons in the acute phase after SAH, while its role in EBI has not been examined. This study was designed to explore the effects of autophagy on EBI post-SAH in rats. A modified endovascular perforating SAH model was established under monitoring of intracranial pressure. Extent of autophagy was regulated by injecting autophagy-regulating drugs (3-methyladenine, wortmannin and rapamycin) 30 min pre-SAH intraventricularly. Simvastatin (20 mg/kg) was prophylactically orally given 14 days before SAH induction. Mortality, neurological scores, brain water content and blood–brain barrier (BBB) permeability were evaluated at 24 h post-SAH. Microtubule-associated protein light chain-3 (LC3 II/I) and beclin-1 were detected for monitoring of autophagy flux. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, expression of cleaved caspase-3 and cytoplasmic histone-associated DNA fragments were used to detect apoptosis. The results showed that mortality was reduced in rapamycin and simvastatin treated animals. When autophagy was inhibited by 3-methyladenine and wortmannin, the neurological scores were decreased, brain water content and BBB permeability were further aggravated and neuronal apoptosis was increased when compared with the SAH animals. Autophagy was further activated by rapamycin and simvastatin, and apoptosis was inhibited and EBI was ameliorated. The present results indicated that activation of autophagy decreased neuronal apoptosis and ameliorated EBI after SAH. Aiming at autophagy may be a potential effective target for preventing EBI after SAH. 相似文献
67.
The objective of this study was to investigate the influence of solids retention time (SRT) on membrane fouling and the characteristics of biomacromolecules. Four identical laboratory-scale membrane bioreactors (MBRs) were operated with SRTs for 10, 20, 40 and 80 days. The results indicated that membrane fouling occurred faster and more readily under short SRTs. Fouling resistance was the primary source of filtration resistance. The modified fouling index (MFI) results suggested that the more ready fouling at short SRTs could be attributed to higher concentrations of soluble microbial products (SMP). Fourier transform infrared (FTIR) spectra indicated that the SRT had a weak influence on the functional groups of the total extracellular polymeric substances (TEPS) and SMP. However, the MBR under a short SRT had more low-molecular-weight (MW) compounds (<1 kDa) and fewer high-MW compounds (>100 kDa). Aromatic protein and tryptophan protein-like substances were the dominant groups in the TEPS and SMP, respectively. 相似文献
68.
Hailan Liu Xi Wu Zizheng Dong Zhiyong Luo Zhenwen Zhao Yan Xu Jian-Ting Zhang 《Journal of lipid research》2013,54(3):776-785
Fatty acid synthase (FASN) is a key enzyme in the synthesis of palmitate, the precursor of major nutritional, energetic, and signaling lipids. FASN expression is upregulated in many human cancers and appears to be important for cancer cell survival. Overexpression of FASN has also been found to associate with poor prognosis and higher risk of recurrence of human cancers. Indeed, elevated FASN expression has been shown to contribute to drug resistance. However, the mechanism of FASN-mediated drug resistance is currently unknown. In this study, we show that FASN overexpression causes resistance to multiple anticancer drugs via inhibiting drug-induced ceramide production, caspase 8 activation, and apoptosis. We also show that FASN overexpression suppresses tumor necrosis factor-α production and nuclear factor-κB activation as well as drug-induced activation of neutral sphingomyelinase. Thus, TNF-α may play an important role in mediating FASN function in drug resistance. 相似文献
69.
Leslie W. Tari Michael Trzoss Daniel C. Bensen Xiaoming Li Zhiyong Chen Thanh Lam Junhu Zhang Christopher J. Creighton Mark L. Cunningham Bryan Kwan Mark Stidham Karen J. Shaw Felice C. Lightstone Sergio E. Wong Toan B. Nguyen Jay Nix John Finn 《Bioorganic & medicinal chemistry letters》2013,23(5):1529-1536
The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity. 相似文献
70.