全文获取类型
收费全文 | 33683篇 |
免费 | 1771篇 |
国内免费 | 41篇 |
专业分类
电工技术 | 252篇 |
综合类 | 21篇 |
化学工业 | 6714篇 |
金属工艺 | 643篇 |
机械仪表 | 713篇 |
建筑科学 | 940篇 |
矿业工程 | 72篇 |
能源动力 | 591篇 |
轻工业 | 5500篇 |
水利工程 | 329篇 |
石油天然气 | 119篇 |
武器工业 | 5篇 |
无线电 | 1281篇 |
一般工业技术 | 5687篇 |
冶金工业 | 8001篇 |
原子能技术 | 135篇 |
自动化技术 | 4492篇 |
出版年
2024年 | 78篇 |
2023年 | 296篇 |
2022年 | 316篇 |
2021年 | 788篇 |
2020年 | 669篇 |
2019年 | 760篇 |
2018年 | 1352篇 |
2017年 | 1322篇 |
2016年 | 1379篇 |
2015年 | 1057篇 |
2014年 | 1236篇 |
2013年 | 2628篇 |
2012年 | 1963篇 |
2011年 | 1773篇 |
2010年 | 1462篇 |
2009年 | 1300篇 |
2008年 | 1270篇 |
2007年 | 1201篇 |
2006年 | 803篇 |
2005年 | 684篇 |
2004年 | 650篇 |
2003年 | 565篇 |
2002年 | 563篇 |
2001年 | 417篇 |
2000年 | 388篇 |
1999年 | 442篇 |
1998年 | 2374篇 |
1997年 | 1624篇 |
1996年 | 1044篇 |
1995年 | 621篇 |
1994年 | 475篇 |
1993年 | 564篇 |
1992年 | 210篇 |
1991年 | 205篇 |
1990年 | 155篇 |
1989年 | 158篇 |
1988年 | 163篇 |
1987年 | 137篇 |
1986年 | 123篇 |
1985年 | 144篇 |
1984年 | 130篇 |
1983年 | 100篇 |
1982年 | 134篇 |
1981年 | 148篇 |
1980年 | 159篇 |
1979年 | 84篇 |
1978年 | 88篇 |
1977年 | 282篇 |
1976年 | 627篇 |
1973年 | 66篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
992.
Frida S. Herrera-Vázquez Dr. Félix Matadamas-Martínez Dr. Rodrigo Aguayo-Ortiz Prof. Laura Dominguez Teresa Ramírez-Apan Prof. Lilián Yépez-Mulia Prof. Francisco Hernández-Luis 《ChemMedChem》2020,15(19):1802-1812
Microtubules are highly dynamic polymers composed of α- and β-tubulin proteins that have been shown to be potential therapeutic targets for the development of anticancer drugs. Currently, a wide variety of chemically diverse agents that bind to β-tubulin have been reported. Nocodazole (NZ) and colchicine (COL) are well-known tubulin-depolymerizing agents that have close binding sites in the β-tubulin. In this study, we designed and synthesized a set of nine 2,4-diaminoquinazoline derivatives that could occupy both NZ and COL binding sites. The synthesized compounds were evaluated for their antiproliferative activities against five cancer cell lines (PC-3, HCT-15, MCF-7, MDA-MB-231, and SK-LU-1), a noncancerous one (COS-7), and peripheral blood mononuclear cells (PBMC). The effect of compounds 4 e and 4 i on tubulin organization and polymerization was analyzed on the SK-LU-1 cell line by indirect immunofluorescence, western blotting, and tubulin polymerization assays. Our results demonstrated that both compounds exert their antiproliferative activity by inhibiting tubulin polymerization. Finally, a possible binding pose of 4 i in the NZ/COL binding site was determined by using molecular docking and molecular dynamics (MD) approaches. To our knowledge, this is the first report of non-N-substituted 2,4-diaminoquinazoline derivatives with the ability to inhibit tubulin polymerization. 相似文献
993.
In solution, amphoteric compounds exist in anionic, uncharged, zwitterionic and cationic forms. The importance of zwitterionic drugs is currently under-represented in the literature. Herein, the acid-base parameters, lipophilicity and solubility of such compounds are discussed to deepen the molecular-level understanding of their pharmacokinetic and pharmacodynamic behaviour. Our recent studies show there are many drug molecules, including thyroid hormones and 5-hydroxytryptophan, the precursor of the neurotransmitter serotonin, for which the contribution of the zwitterionic microspecies to the overall lipophilicity exceeds that of the uncharged one, which is of higher individual lipophilicity, but occurs in much lower concentration. The second part of the minireview highlights the most important zwitterionic compounds in therapy, grouped into therapeutic classes. The importance of the charge of the molecules is emphasized in their binding to the target molecules. 相似文献
994.
995.
996.
997.
998.
Ricardo Martínez-Corona Gerardo Vázquez Marrufo Carlos Cortés Penagos Luis Alberto Madrigal-Pérez Juan Carlos González-Hernández 《Yeast (Chichester, England)》2020,37(1):149-162
Lipases are hydrolytic enzymes that break the ester bonds of triglycerides, generating free fatty acids and glycerol. Extracellular lipase activity has been reported for the nonconventional yeast Kluyveromyces marxianus, grown in olive oil as a substrate, and the presence of at least eight putative lipases has been detected in its genome. However, to date, there is no experimental evidence on the physiological role of the putative lipases nor their structural and catalytic properties. In this study, a bioinformatic analysis of the genes of the putative lipases from K. marxianus L-2029 was performed, particularly identifying and characterizing the extracellular expected enzymes, due to their biotechnological relevance. The amino acid sequence of 10 putative lipases, obtained by in silico translation, ranged between 389 and 773 amino acids. Two of the analysed putative proteins showed a signal peptide, 25 and 33 amino acids long for KmYJR107Wp and KmLIP3p, and a molecular weight of 44.53 and 58.23 kDa, respectively. The amino acid alignment of KmLIP3p and KmYJR107Wp with the crystallized lipases from a patatin and the YlLip2 lipase from Yarrowia lipolytica, respectively, revealed the presence of the hydrolase characteristic motifs. From the 3D models of putative extracellular K. marxianus L-2029 lipases, the conserved pentapeptide of each was determined, being GTSMG for KmLIP3p and GHSLG for KmYJR107Wp; besides, the genes of these two enzymes (LIP3 and YJR107W) are apparently regulated by oleate response elements. The phylogenetic analysis of all K. marxianus lipases revealed evolutionary affinities with lipases from abH15.03, abH23.01, and abH23.02 families. 相似文献
999.
The fission yeast Schizosaccharomyces pombe is an important model organism for the study of fundamental questions in eukaryotic cell and molecular biology. A plethora of cellular processes are membrane associated and/or dependent on the proper functioning of cellular membranes. Phospholipids are not only the basic building blocks of cellular membranes; they also serve as precursors to numerous signaling molecules. In this review, we describe the biosynthetic pathways leading to major S. pombe phospholipids, how these pathways are regulated, and what is known about degradation and turnover of fission yeast phospholipids. This review also addresses the synthesis, regulation and the role of water-soluble phospholipid precursors. The last chapter of the review is devoted to the use of S. pombe for the biotechnological production of value-added lipid molecules. 相似文献
1000.
Dr. Camila M. Crnkovic Dr. Jana Braesel Dr. Aleksej Krunic Prof. Dr. Alessandra S. Eustáquio Prof. Dr. Jimmy Orjala 《Chembiochem : a European journal of chemical biology》2020,21(6):845-852
Cyanobactins are a large family of cyanobacterial ribosomally synthesized and post-translationally modified peptides (RiPPs) often associated with biological activities, such as cytotoxicity, antiviral, and antimalarial activities. They are traditionally described as cyclic molecules containing heterocyclized amino acids. However, this definition has been recently challenged by the discovery of short, linear cyanobactins containing three to five amino acids as well as cyanobactins containing no heterocyclized residues. Herein we report the discovery of scytodecamide ( 1 ) from the freshwater cyanobacterium Scytonema sp. UIC 10036. Structural elucidation based on mass spectrometry, 1D and 2D NMR spectroscopy, and Marfey's method revealed 1 to be a linear decapeptide with an N-terminal N-methylation and a C-terminal amidation. The genome of Scytonema sp. UIC 10036 was sequenced, and bioinformatic analysis revealed a cyanobactin-like biosynthetic gene cluster consistent with the structure of 1 . The discovery of 1 as a novel linear peptide containing an N-terminal N-methylation and a C-terminal amidation expands the chemical and genetic diversity of the cyanobactin family of compounds. 相似文献