全文获取类型
收费全文 | 511篇 |
免费 | 23篇 |
国内免费 | 22篇 |
专业分类
电工技术 | 8篇 |
综合类 | 18篇 |
化学工业 | 187篇 |
金属工艺 | 32篇 |
机械仪表 | 39篇 |
建筑科学 | 10篇 |
矿业工程 | 32篇 |
能源动力 | 5篇 |
轻工业 | 123篇 |
水利工程 | 3篇 |
石油天然气 | 7篇 |
武器工业 | 1篇 |
无线电 | 5篇 |
一般工业技术 | 16篇 |
冶金工业 | 42篇 |
原子能技术 | 17篇 |
自动化技术 | 11篇 |
出版年
2024年 | 3篇 |
2023年 | 6篇 |
2022年 | 52篇 |
2021年 | 69篇 |
2020年 | 19篇 |
2019年 | 14篇 |
2018年 | 14篇 |
2017年 | 9篇 |
2016年 | 20篇 |
2015年 | 18篇 |
2014年 | 29篇 |
2013年 | 28篇 |
2012年 | 24篇 |
2011年 | 34篇 |
2010年 | 21篇 |
2009年 | 18篇 |
2008年 | 20篇 |
2007年 | 23篇 |
2006年 | 13篇 |
2005年 | 17篇 |
2004年 | 19篇 |
2003年 | 13篇 |
2002年 | 15篇 |
2001年 | 14篇 |
2000年 | 14篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 2篇 |
排序方式: 共有556条查询结果,搜索用时 15 毫秒
1.
Anne-Margarethe Enge Florian Kaltner Christoph Gottschalk Albert Braeuning Stefanie Hessel-Pras 《International journal of molecular sciences》2021,22(8)
1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na+/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics. 相似文献
2.
3.
在顺丁橡胶后处理生产线上,用处行开发的新型交替运输取代原有运输机。试用结果表明,采用新型交替运输机后,胶块的导向到位率由70%提高到98%;减轻了劳动强度,提出了生产开工率,运行周期可达1a以上。 相似文献
4.
Amir Mohammadzadeh Pter P. Lakatos Mihly Balogh Ferenc Zdor Dvid rpd Kardi Zoltn S. Zdori Kornl Kirly Anna Rita Galambos Szilvia Barsi Pl Riba Sndor Benyhe Lszl Kles Tams Tbi va Szk Laszlo G. Harsing Jr. Mahmoud Al-Khrasani 《International journal of molecular sciences》2021,22(5)
The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP. 相似文献
5.
Eleni Papakonstantinou Dimitrios Vlachakis Trias Thireou Panayiotis G. Vlachoyiannopoulos Elias Eliopoulos 《International journal of molecular sciences》2021,22(6)
Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy. 相似文献
6.
James I. Mitchell-White Thomas Stockner Nicholas Holliday Stephen J. Briddon Ian D. Kerr 《International journal of molecular sciences》2021,22(6)
The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates. 相似文献
7.
Thomas M. Ackermann Dr. Lars Allmendinger Dr. Georg Höfner Prof. Dr. Klaus T. Wanner 《ChemMedChem》2021,16(1):199-215
This study describes the first binding assay for glycine transporter 2 (GlyT2) following the concept of MS Binding Assays. The selective GlyT2 inhibitor Org25543 was employed as a reporter ligand and it was quantified with a highly sensitive and rapid LC-ESI-MS/MS method. Binding of Org25543 at GlyT2 was characterized in kinetic and saturation experiments with an off-rate of 7.07×10−3 s−1, an on-rate of 1.01×106 M−1 s−1, and an equilibrium dissociation constant of 7.45 nM. Furthermore, the inhibitory constants of 19 GlyT ligands were determined in competition experiments. The validity of the GlyT2 affinities determined with the binding assay was examined by a comparison with published inhibitory potencies from various functional assays. With the capability for affinity determination towards GlyT2 the developed MS Binding Assays provide the first tool for affinity profiling of potential ligands and it represents a valuable new alternative to functional assays addressing GlyT2. 相似文献
8.
9.
垃圾邮件过滤是当前计算机领域的热点问题。文章针对目前网页抓取分析技术不能深入分析网页内容的缺点,提出了一种优化的网页抓取分析技术,能够对网页提取一些更为深入的特征,并以此为基础,完成了基于网页抓取分析和统计压缩模型的垃圾邮件过滤系统的设计与实现。文章创新地提取出5种新的特征,实验结果表明,这些特征对于增高TPR(True Positive Rate,真正类率),降低FPR(False Positive Rate,负正类率),提升垃圾邮件过滤的效率和准确性具有显著作用。 相似文献
10.
Li YF Polgar O Okada M Esser L Bates SE Xia D 《Journal of molecular graphics & modelling》2007,25(6):837-851
The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC transporters with potential clinical importance as a mediator of multidrug resistance. We carried out a homology and knowledge-based, and mutationally improved molecular modeling study to establish a much needed structural framework for the protein, which could serve as guidance for further genetic, biochemical, and structural analyses. Based on homology with known structures of both full-length and nucleotide-binding domains (NBD) of ABC transporters and structural knowledge of integral membrane proteins, an initial model of ABCG2 was established. Subsequent refinement to conform to the lipophilic index distributions in the transmembrane domain (TMD) and to the results of site-directed mutagenesis experiments led to an improved model. The complete ABCG2 model consists of two identical subunits facing each other in a closed conformation. The dimeric interface in the nucleotide-binding domain (NBD) involves a characteristic nucleotide sandwich and the interface in the TMD consists of the TM helices 1–3 of one subunit and the helices 5 and 6 of the other. The interface between the NBD and the TMD is bridged by the conserved structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the terminal β-strand (S6) of the central β-sheet in the NBD. The apparent flexibility of the ICD1 may play a role in transmitting conformational changes from the NBD to the TMD or from the TMD to the NBD. 相似文献