全文获取类型
收费全文 | 18766篇 |
免费 | 2854篇 |
国内免费 | 10篇 |
专业分类
电工技术 | 1433篇 |
综合类 | 866篇 |
化学工业 | 9416篇 |
金属工艺 | 294篇 |
机械仪表 | 423篇 |
建筑科学 | 712篇 |
矿业工程 | 181篇 |
能源动力 | 150篇 |
轻工业 | 1751篇 |
水利工程 | 127篇 |
石油天然气 | 69篇 |
武器工业 | 1篇 |
无线电 | 422篇 |
一般工业技术 | 3407篇 |
冶金工业 | 185篇 |
原子能技术 | 48篇 |
自动化技术 | 2145篇 |
出版年
2023年 | 675篇 |
2022年 | 342篇 |
2021年 | 741篇 |
2020年 | 736篇 |
2019年 | 623篇 |
2018年 | 608篇 |
2017年 | 406篇 |
2016年 | 656篇 |
2015年 | 846篇 |
2014年 | 885篇 |
2013年 | 1549篇 |
2012年 | 592篇 |
2011年 | 469篇 |
2010年 | 876篇 |
2009年 | 999篇 |
2008年 | 454篇 |
2007年 | 414篇 |
2006年 | 310篇 |
2005年 | 323篇 |
2004年 | 341篇 |
2003年 | 309篇 |
2002年 | 267篇 |
2001年 | 173篇 |
1998年 | 234篇 |
1997年 | 160篇 |
1996年 | 238篇 |
1995年 | 216篇 |
1994年 | 191篇 |
1993年 | 254篇 |
1992年 | 179篇 |
1991年 | 156篇 |
1990年 | 178篇 |
1989年 | 201篇 |
1988年 | 163篇 |
1987年 | 195篇 |
1986年 | 205篇 |
1985年 | 182篇 |
1984年 | 193篇 |
1983年 | 193篇 |
1982年 | 179篇 |
1981年 | 225篇 |
1980年 | 176篇 |
1979年 | 186篇 |
1977年 | 162篇 |
1976年 | 166篇 |
1975年 | 223篇 |
1974年 | 201篇 |
1973年 | 381篇 |
1972年 | 227篇 |
1971年 | 157篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
61.
Yuanfang Tao Xin Ji Dr. Jian Zhang Yue Jin Nannan Wang Prof. Yubing Si Prof. Weili Zhao 《Chembiochem : a European journal of chemical biology》2020,21(21):3131-3136
Near-infrared (NIR) fluorescent probes are very significant for detecting cysteine in biological systems. Herein, we report a highly selective and sensitive NIR turn-on fluorescent probe (BDP-NIR) based on BODIPY with large Stokes shift (105 nm) for detecting Cys. We clarified the sensing mechanism based on the different thiol-induced SNAr substitution/rearrangement reaction of the probe with cysteine and homocysteine/glutathione, which leads to the corresponding amino- and thiol-BODIPY dyes with distinct photophysical properties. Moreover, a novel mechanism of fluorescence quenching was demonstrated by density functional theory calculation. The reason for the fluorescence quenching of the probe might be intersystem crossing (from singlet to triplet excited state). Moreover, BDP-NIR had a high linear dynamic range of 0–500 μM, which was promising for detecting cysteine quantificationally. Significantly, BDP-NIR was capable of sensing endogenous cysteine in living cells and in vivo. 相似文献
62.
63.
Freddy A. Bernal Dr. Marcel Kaiser Prof. Dr. Bernhard Wünsch Prof. Dr. Thomas J. Schmidt 《ChemMedChem》2020,15(1):68-78
Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model. 相似文献
64.
Dr. Ivan A. Yaremenko Dr. Paolo Coghi Parichat Prommana Congling Qiu Peter S. Radulov Yuanqing Qu Yulia Yu. Belyakova Dr. Enrico Zanforlin Dr. Vladimir A. Kokorekin Yuki Yu Jun Wu Prof. Fabrice Fleury Dr. Chairat Uthaipibull Dr. Vincent Kam Wai Wong Prof. Alexander O. Terent'ev 《ChemMedChem》2020,15(13):1118-1127
This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC50=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma. 相似文献
65.
66.
Prof. Dr. Hans-René Bjørsvik Prof. Dr. Bjørn Tore Gjertsen Dr. Vijayaragavan Elumalai 《ChemMedChem》2020,15(10):862-870
A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC50<10−4 M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines. 相似文献
67.
Alice Maurer Prof. Dr. Florian P. Seebeck 《Chembiochem : a European journal of chemical biology》2020,21(20):2908-2911
Ergothioneine has emerged as a crucial cytoprotectant in the pathogenic lifestyle of Mycobacterium tuberculosis. Production of this antioxidant from primary metabolites may be regulated by phosphorylation of Thr213 in the active site of the methyltransferase EgtD. The structure of mycobacterial EgtD suggests that this post-translational modification would require a large-scale change in conformation to make the active-site residue accessible to a protein kinase. In this report, we show that, under in vitro conditions, EgtD is not a substrate of protein kinase PknD. 相似文献
68.
69.
Dr. Hui Qiu Richard Caldwell Dr. Lesley Liu-Bujalski Dr. Andreas Goutopoulos Reinaldo Jones Justin Potnick Dr. Brian Sherer Dr. Andrew Bender Dr. Roland Grenningloh Dr. Daigen Xu Dr. Anna Gardberg Dr. Igor Mochalkin Dr. Theresa Johnson Dr. Ariele Viacava Follis Jared Head Dr. Federica Morandi 《ChemMedChem》2019,14(2):217-223
Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. 相似文献
70.
Dr. Manuel Nieto-Domínguez Dr. Pablo I. Nikel 《Chembiochem : a European journal of chemical biology》2020,21(18):2551-2571
The diversity of life relies on a handful of chemical elements (carbon, oxygen, hydrogen, nitrogen, sulfur and phosphorus) as part of essential building blocks; some other atoms are needed to a lesser extent, but most of the remaining elements are excluded from biology. This circumstance limits the scope of biochemical reactions in extant metabolism – yet it offers a phenomenal playground for synthetic biology. Xenobiology aims to bring novel bricks to life that could be exploited for (xeno)metabolite synthesis. In particular, the assembly of novel pathways engineered to handle nonbiological elements (neometabolism) will broaden chemical space beyond the reach of natural evolution. In this review, xeno-elements that could be blended into nature's biosynthetic portfolio are discussed together with their physicochemical properties and tools and strategies to incorporate them into biochemistry. We argue that current bioproduction methods can be revolutionized by bridging xenobiology and neometabolism for the synthesis of new-to-nature molecules, such as organohalides. 相似文献