全文获取类型
收费全文 | 3014篇 |
免费 | 358篇 |
国内免费 | 65篇 |
专业分类
综合类 | 84篇 |
化学工业 | 952篇 |
金属工艺 | 21篇 |
机械仪表 | 69篇 |
建筑科学 | 14篇 |
能源动力 | 1篇 |
轻工业 | 1962篇 |
水利工程 | 1篇 |
石油天然气 | 7篇 |
无线电 | 70篇 |
一般工业技术 | 192篇 |
冶金工业 | 5篇 |
原子能技术 | 22篇 |
自动化技术 | 37篇 |
出版年
2024年 | 30篇 |
2023年 | 109篇 |
2022年 | 247篇 |
2021年 | 318篇 |
2020年 | 185篇 |
2019年 | 170篇 |
2018年 | 154篇 |
2017年 | 162篇 |
2016年 | 151篇 |
2015年 | 161篇 |
2014年 | 138篇 |
2013年 | 196篇 |
2012年 | 244篇 |
2011年 | 209篇 |
2010年 | 129篇 |
2009年 | 135篇 |
2008年 | 107篇 |
2007年 | 104篇 |
2006年 | 115篇 |
2005年 | 86篇 |
2004年 | 60篇 |
2003年 | 53篇 |
2002年 | 42篇 |
2001年 | 24篇 |
2000年 | 10篇 |
1999年 | 14篇 |
1998年 | 16篇 |
1997年 | 7篇 |
1996年 | 11篇 |
1995年 | 3篇 |
1994年 | 7篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1980年 | 5篇 |
1977年 | 1篇 |
排序方式: 共有3437条查询结果,搜索用时 15 毫秒
991.
Esra Yuca Sheng-Xue Xie Linyong Song Kyle Boone Nilan Kamathewatta Sarah K. Woolfolk Philip Elrod Paulette Spencer Candan Tamerler 《International journal of molecular sciences》2021,22(12)
Resin-based composite materials have been widely used in restorative dental materials due to their aesthetic, mechanical, and physical properties. However, they still encounter clinical shortcomings mainly due to recurrent decay that develops at the composite-tooth interface. The low-viscosity adhesive that bonds the composite to the tooth is intended to seal this interface, but the adhesive seal is inherently defective and readily damaged by acids, enzymes, and oral fluids. Bacteria infiltrate the resulting gaps at the composite-tooth interface and bacterial by-products demineralize the tooth and erode the adhesive. These activities lead to wider and deeper gaps that provide an ideal environment for bacteria to proliferate. This complex degradation process mediated by several biological and environmental factors damages the tooth, destroys the adhesive seal, and ultimately, leads to failure of the composite restoration. This paper describes a co-tethered dual peptide-polymer system to address composite-tooth interface vulnerability. The adhesive system incorporates an antimicrobial peptide to inhibit bacterial attack and a hydroxyapatite-binding peptide to promote remineralization of damaged tooth structure. A designer spacer sequence was incorporated into each peptide sequence to not only provide a conjugation site for methacrylate (MA) monomer but also to retain active peptide conformations and enhance the display of the peptides in the material. The resulting MA-antimicrobial peptides and MA-remineralization peptides were copolymerized into dental adhesives formulations. The results on the adhesive system composed of co-tethered peptides demonstrated both strong metabolic inhibition of S. mutans and localized calcium phosphate remineralization. Overall, the result offers a reconfigurable and tunable peptide-polymer hybrid system as next-generation adhesives to address composite-tooth interface vulnerability. 相似文献
992.
993.
Yongwei Zhao Y. T. Candace Ho Dr. Julien Tailhades Prof. Dr. Max Cryle 《Chembiochem : a European journal of chemical biology》2021,22(1):43-51
The glycopeptide antibiotics (GPAs) are a fascinating example of complex natural product biosynthesis, with the nonribosomal synthesis of the peptide core coupled to a cytochrome P450-mediated cyclisation cascade that crosslinks aromatic side chains within this peptide. Given that the challenges associated with the synthesis of GPAs stems from their highly crosslinked structure, there is great interest in understanding how biosynthesis accomplishes this challenging set of transformations. In this regard, the use of in vitro experiments has delivered important insights into this process, including the identification of the unique role of the X-domain as a platform for P450 recruitment. In this minireview, we present an analysis of the results of in vitro studies into the GPA cyclisation cascade that have demonstrated both the tolerances and limitations of this process for modified substrates, and in turn developed rules for the future reengineering of this important antibiotic class. 相似文献
994.
Lennart Nicke Philip Horx Ronny Müller Dr. Sylvia Els-Heindl Prof. Dr. Armin Geyer 《Chembiochem : a European journal of chemical biology》2021,22(2):330-335
A generalized synthetic strategy is proposed here for the synthesis of asymmetric β-indoylated amino acids by 8-aminoquinoline (8AQ)-directed C(sp3)-H functionalization of suitably protected precursors. Peptides containing one of the four stereoisomers of (indol-3-yl)-3-phenylalanine at position 2 of the parent peptide KwFwLL-NH2 (w=d -Trp) cover a wide range of activities as ghrelin receptor inverse agonists, among them the most active described until now. This application exemplarily shows how β-indoylated amino acids can be used for the systematic variation of the position of an indole group in a bioactive peptide. 相似文献
995.
Self-assembly peptide materials have promoted the development of science research including life science, optics, medicine, and catalysis over the past two decades. Especially in tumor treatment, peptide self-assembly strategies have exhibited promising potential by their high degree of biocompatibility, construction modularization, and diversity in structure controllability. Driven by physical and chemical triggers, peptides can self-assemble in vivo to form fibers, spheres, hydrogels, or ribbons to achieve predeterminate biological functions. Peptide self-assembly triggered by chemical reactions provides superior specificity and intelligent responsiveness to produce assembly-induced biological effects in target regions. Herein, from the perspective of triggers of peptide assembly, we briefly review the applications of in vivo peptide self-assembly strategies for tumor treatment, including tumor-pathology-factor-induced chemical reactions and bio-orthogonal reactions 相似文献
996.
997.
以构建好的人胸腺素α1基因工程菌为研究材料,研究影响DsbA-胸腺素α1融合蛋白分泌效率的因素,优化信号肽酶表达得到阻遏的培养条件,获得含带信号肽DsbA-胸腺素α1融合蛋白的菌体,破碎细胞后利用疏水层析与Ni2 螯合亲和层析进行目标蛋白分离纯化,获得较高纯度底物蛋白(信号肽DsbA-胸腺素α1融合蛋白,其分子量约为34 kD),为进一步研究及分离纯化DsbA信号肽酶创造条件. 相似文献
998.
史嘉玮 《武汉理工大学学报(材料科学英文版)》2007,(4)
Porcine aortic valves were decellularized with trypsinase/EDTA and Triton-100.With the help of a coupling reagent Sulfo-LC-SPDP,the biological valve scaffolds were immobilized with one of RGD (arginine-glycine-aspartic acid)containing peptides,called GRGDSPC peptide.Myofibroblasts harvested from rats were seeded onto them.Based on the spectra of X-ray photoelectron spectroscopy,we could find conjugation of GRGDSPC peptide and the scaffolds.Cell count by both microscopy and MTT assay showed that myofibroblasts were easier to adhere to the modified scaffolds.It is proved that it is feasible to immobilize RGD peptides onto decellularized valve scaffolds,and effective to promote cell adhesion,which is beneficial for constructing tissue engineering heart valves in vitro. 相似文献
999.
Lingdi Nie Liwen Jiang John P. Quinn Blair D. Grubb Minyan Wang 《International journal of molecular sciences》2021,22(22)
Transient receptor potential ankyrin 1 (TRPA1) plays a role in migraine and is proposed as a promising target for migraine therapy. However, TRPA1-induced signaling in migraine pathogenesis is poorly understood. In this study, we explored the hypothesis that Src family kinases (SFKs) transmit TRPA1 signaling in regulating cortical spreading depression (CSD), calcitonin gene-related peptide (CGRP) release and neuroinflammation. CSD was monitored in mouse brain slices via intrinsic optical imaging, and in rats using electrophysiology. CGRP level and IL-1β gene expression in mouse trigeminal ganglia (TG) was detected using Enzyme-linked Immunosorbent Assay and Quantitative Polymerase Chain Reaction respectively. The results showed a SFKs activator, pYEEI (EPQY(PO3H2)EEEIPIYL), reversed the reduced cortical susceptibility to CSD by an anti-TRPA1 antibody in mouse brain slices. Additionally, the increased cytosolic phosphorylated SFKs at Y416 induced by CSD in rat ipsilateral cerebral cortices was attenuated by pretreatment of the anti-TRPA1 antibody perfused into contralateral ventricles. In mouse TG, a SFKs inhibitor, saracatinib, restored the CGRP release and IL-1β mRNA level increased by a TRPA1 activator, umbellulone. Moreover, umbellulone promoted SFKs phosphorylation, which was reduced by a PKA inhibitor, PKI (14–22) Amide. These data reveal a novel mechanism of migraine pathogenesis by which TRPA1 transmits signaling to SFKs via PKA facilitating CSD susceptibility and trigeminovascular system sensitization. 相似文献
1000.
Feng Guo Junfeng Ke Zhengdong Fu Wenzhao Han Liping Wang 《International journal of molecular sciences》2021,22(24)
Cell penetrating peptides (CPPs) are peptides that can directly adapt to cell membranes and then permeate into cells. CPPs are usually covalently linked to the surface of nanocarriers to endow their permeability to the whole system. However, hybrids with lipids or polymers make the metabolism much more sophisticated and even more difficult to determine. In this study, we present a continuous sequence of 18 amino acids (FFAARTMIWY(d-P)GAWYKRI). It forms nanospheres around 170 nm, which increase slightly after loading with siRNA and DOX. Notably, it can be internalized by cancer cells mainly through electronic interactions and PD-L1-mediated endocytosis. Compared with poly-l-lysine and polyethyleneimine, it has a much higher efficiency (about four times) of gene transduction while lowering toxicity. In the treatment of cancer, it causes apoptosis (21%) and inhibits the expression of SURVIVIN protein in vitro. In vivo, it shows good biocompatibility as there are no changes in mice’s body weight. When administering peptide-siRNA-DOX, tumor growth is inhibited the most (about three times). These results above prove the sequence to be a good candidate for gene therapy and drug delivery. 相似文献