全文获取类型
收费全文 | 11450篇 |
免费 | 2303篇 |
国内免费 | 1篇 |
专业分类
电工技术 | 584篇 |
综合类 | 651篇 |
化学工业 | 7655篇 |
金属工艺 | 127篇 |
机械仪表 | 86篇 |
建筑科学 | 395篇 |
矿业工程 | 37篇 |
能源动力 | 82篇 |
轻工业 | 699篇 |
水利工程 | 32篇 |
石油天然气 | 8篇 |
武器工业 | 1篇 |
无线电 | 179篇 |
一般工业技术 | 1830篇 |
冶金工业 | 214篇 |
原子能技术 | 13篇 |
自动化技术 | 1161篇 |
出版年
2023年 | 553篇 |
2022年 | 439篇 |
2021年 | 745篇 |
2020年 | 641篇 |
2019年 | 511篇 |
2018年 | 493篇 |
2017年 | 359篇 |
2016年 | 546篇 |
2015年 | 642篇 |
2014年 | 671篇 |
2013年 | 904篇 |
2012年 | 467篇 |
2011年 | 390篇 |
2010年 | 669篇 |
2009年 | 764篇 |
2008年 | 357篇 |
2007年 | 286篇 |
2006年 | 167篇 |
2005年 | 194篇 |
2004年 | 240篇 |
2003年 | 195篇 |
2002年 | 216篇 |
2001年 | 106篇 |
1999年 | 83篇 |
1998年 | 126篇 |
1997年 | 82篇 |
1996年 | 105篇 |
1995年 | 111篇 |
1994年 | 92篇 |
1993年 | 140篇 |
1992年 | 95篇 |
1991年 | 82篇 |
1990年 | 89篇 |
1989年 | 93篇 |
1988年 | 76篇 |
1987年 | 94篇 |
1986年 | 105篇 |
1985年 | 93篇 |
1984年 | 84篇 |
1983年 | 106篇 |
1982年 | 82篇 |
1981年 | 113篇 |
1980年 | 88篇 |
1979年 | 69篇 |
1977年 | 72篇 |
1976年 | 55篇 |
1975年 | 68篇 |
1974年 | 70篇 |
1973年 | 135篇 |
1972年 | 77篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Prof. Andrea Baier Dr. Anne Kokel Dr. William Horton Ewa Gizińska Dr. Garima Pandey Prof. Ryszard Szyszka Prof. Béla Török Prof. Marianna Török 《ChemMedChem》2021,16(12):1927-1932
A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4-N(CH3)2 residue or perfluorinated phenyl rings showed high activity in the radical-scavenging assays and possess nanomolar IC50 values in the kinase assays. 相似文献
2.
Paola Leonor Quan Marina Sabat-Bresc Yanru Guo Margarita Martín Gabriel Gastaminza 《International journal of molecular sciences》2021,22(9)
Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease. 相似文献
3.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
4.
Dr. Yibin Zhang Dr. Shuai Xia Shulin Wan Tessa E. Steenwinkel Tara Vohs Prof. Rudy L. Luck Prof. Thomas Werner Prof. Haiying Liu 《Chembiochem : a European journal of chemical biology》2021,22(13):2282-2291
Abnormal levels of glutathione, a cellular antioxidant, can lead to a variety of diseases. We have constructed a near-infrared ratiometric fluorescent probe to detect glutathione concentrations in biological samples. The probe consists of a coumarin donor, which is connected through a disulfide-tethered linker to a rhodamine acceptor. Under the excitation of the coumarin donor at 405 nm, the probe shows weak visible fluorescence of the coumarin donor at 470 nm and strong near-infrared fluorescence of the rhodamine acceptor at 652 nm due to efficient Forster resonance energy transfer (FRET) from the donor to the acceptor. Glutathione breaks the disulfide bond through reduction, which results in a dramatic increase in coumarin fluorescence and a corresponding decrease in rhodamine fluorescence. The probe possesses excellent cell permeability, biocompatibility, and good ratiometric fluorescence responses to glutathione and cysteine with a self-calibration capability. The probe was utilized to ratiometrically visualize glutathione concentration alterations in HeLa cells and Drosophila melanogaster larvae. 相似文献
5.
Dr. Thomas Le Bihan Dr. Cathryn H. S. Driver Dr. Thomas Ebenhan Dr. Nathalie Le Bris Dr. Jan Rijn Zeevaart Prof. Dr. Raphaël Tripier 《ChemMedChem》2021,16(5):809-821
An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2Mal, has been synthesized and studied for in vivo 64Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [64Cu]Cu-GluCAB-2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64Cu]Cu-GluCAB-2Mal and previous-generation [64Cu]Cu-GluCAB-1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64Cu]Cu-GluCAB-2Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [64Cu]Cu-Glu-CAB-2Mal. 相似文献
6.
7.
Dr. Sandra Liebscher Dr. Sebastian Mathea Dr. Tobias Aumüller Dr. Andreas Pech Prof. Dr. Frank Bordusa 《Chembiochem : a European journal of chemical biology》2021,22(7):1201-1204
Fluorescent fusion proteins are powerful tools for studying biological processes in living cells, but universal application is limited due to the voluminous size of those tags, which might have an impact on the folding, localization or even the biological function of the target protein. The designed biocatalyst trypsiligase enables site-directed linkage of small-sized fluorescence dyes on the N terminus of integral target proteins located in the outer membrane of living cells through a stable native peptide bond. The function of the approach was tested by using the examples of covalent derivatization of the transmembrane proteins CD147 as well as the EGF receptor, both presented on human HeLa cells. Specific trypsiligase recognition of the site of linkage was mediated by the dipeptide sequence Arg-His added to the proteins’ native N termini, pointing outside the cell membrane. The labeling procedure takes only about 5 minutes, as demonstrated for couplings of the fluorescence dye tetramethyl rhodamine and the affinity label biotin as well. 相似文献
8.
Marco Bocchetti Maria Grazia Ferraro Filippo Ricciardiello Alessandro Ottaiano Amalia Luce Alessia Maria Cossu Marianna Scrima Wing-Yan Leung Marianna Abate Paola Stiuso Michele Caraglia Silvia Zappavigna Tung On Yau 《International journal of molecular sciences》2021,22(8)
Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18–25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes’ expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment. 相似文献
9.
Dr. Qian Wang Xinli Fan Nannan Jing Han Zhao Dr. Lijia Yu Prof. Xinjing Tang 《Chembiochem : a European journal of chemical biology》2021,22(11):1901-1907
Small interfering RNA (siRNA) can effectively silence target genes through Argonate 2 (Ago2)-induced RNA interference (RNAi). It is very important to control siRNA activity in both spatial and temporal modes. Among different masking strategies, photocaging can be used to regulate gene expression through light irradiation with spatiotemporal and dose-dependent resolution. Many different caging strategies and caging groups have been reported for light-activated siRNA gene silencing. Herein, we describe a novel caging strategy that increases the blocking effect of RISC complex formation/process through host/guest (including ligand/receptor) interactions, thereby enhancing the inhibition of caged siRNA activity until light activation. This strategy can be used as a general approach to design caged siRNAs for the photomodulation of gene silencing of exogenous and endogenous genes. 相似文献
10.
Dr. Ying Wang Prof. Dr. Andrew Ewing 《Chembiochem : a European journal of chemical biology》2021,22(5):807-813
Exocytosis plays an essential role in the communication between cells in the nervous system. Understanding the regulation of neurotransmitter release during exocytosis and the amount of neurotransmitter content that is stored in vesicles is of importance, as it provides fundamental insights to understand how the brain works and how neurons elicit a certain behavior. In this minireview, we summarize recent progress in amperometric measurements for monitoring exocytosis in single cells and electrochemical cytometry measurements of vesicular neurotransmitter content in individual vesicles. Important steps have increased our understanding of the different mechanisms of exocytosis. Increasing evidence is firmly establishing that partial release is the primary mechanism of release in multiple cell types. 相似文献