全文获取类型
收费全文 | 6506篇 |
免费 | 423篇 |
国内免费 | 11篇 |
专业分类
电工技术 | 58篇 |
综合类 | 10篇 |
化学工业 | 2848篇 |
金属工艺 | 78篇 |
机械仪表 | 86篇 |
建筑科学 | 264篇 |
矿业工程 | 35篇 |
能源动力 | 161篇 |
轻工业 | 1146篇 |
水利工程 | 41篇 |
石油天然气 | 35篇 |
无线电 | 261篇 |
一般工业技术 | 939篇 |
冶金工业 | 327篇 |
原子能技术 | 17篇 |
自动化技术 | 634篇 |
出版年
2024年 | 16篇 |
2023年 | 113篇 |
2022年 | 673篇 |
2021年 | 779篇 |
2020年 | 233篇 |
2019年 | 212篇 |
2018年 | 257篇 |
2017年 | 209篇 |
2016年 | 263篇 |
2015年 | 226篇 |
2014年 | 274篇 |
2013年 | 454篇 |
2012年 | 379篇 |
2011年 | 418篇 |
2010年 | 279篇 |
2009年 | 277篇 |
2008年 | 277篇 |
2007年 | 243篇 |
2006年 | 215篇 |
2005年 | 153篇 |
2004年 | 139篇 |
2003年 | 113篇 |
2002年 | 99篇 |
2001年 | 55篇 |
2000年 | 47篇 |
1999年 | 55篇 |
1998年 | 36篇 |
1997年 | 43篇 |
1996年 | 43篇 |
1995年 | 35篇 |
1994年 | 36篇 |
1993年 | 31篇 |
1992年 | 27篇 |
1991年 | 16篇 |
1990年 | 23篇 |
1989年 | 11篇 |
1988年 | 18篇 |
1987年 | 14篇 |
1986年 | 7篇 |
1985年 | 18篇 |
1984年 | 16篇 |
1983年 | 17篇 |
1982年 | 6篇 |
1981年 | 11篇 |
1980年 | 11篇 |
1979年 | 10篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1974年 | 4篇 |
1966年 | 5篇 |
排序方式: 共有6940条查询结果,搜索用时 15 毫秒
141.
Aleksandr S. Kazachenko Feride Akman Natalya Yu. Vasilieva Noureddine Issaoui Yuriy N. Malyar Aleksandr A. Kondrasenko Valentina S. Borovkova Angelina V. Miroshnikova Anna S. Kazachenko Omar Al-Dossary Marek J. Wojcik Yaroslava D. Berezhnaya Evgeniy V. Elsufev 《International journal of molecular sciences》2022,23(3)
Betulin is an important triterpenoid substance isolated from birch bark, which, together with its sulfates, exhibits important bioactive properties. We report on a newly developed method of betulin sulfation with sulfamic acid in pyridine in the presence of an Amberlyst®15 solid acid catalyst. It has been shown that this catalyst remains stable when being repeatedly (up to four cycles) used and ensures obtaining of sulfated betulin with a sulfur content of ~10%. The introduction of the sulfate group into the betulin molecule has been proven by Fourier-transform infrared, ultraviolet-visible, and nuclear magnetic resonance spectroscopy. The Fourier-transform infrared (FTIR) spectra contain absorption bands at 1249 and 835–841 cm−1; in the UV spectra, the peak intensity decreases; and, in the nuclear magnetic resonance (NMR) spectra, of betulin disulfate, carbons С3 and С28 are completely shifted to the weak-field region (to 88.21 and 67.32 ppm, respectively) with respect to betulin. Using the potentiometric titration method, the product of acidity constants K1 and K2 of a solution of the betulin disulfate H+ form has been found to be 3.86 × 10–6 ± 0.004. It has been demonstrated by the thermal analysis that betulin and the betulin disulfate sodium salt are stable at temperatures of up to 240 and 220 °C, respectively. The density functional theory method has been used to obtain data on the most stable conformations, molecular electrostatic potential, frontier molecular orbitals, and mulliken atomic charges of betulin and betulin disulfate and to calculate the spectral characteristics of initial and sulfated betulin, which agree well with the experimental data. 相似文献
142.
Dr. Markella Konstantinidou Francesca Magari Fandi Sutanto Dr. Jörg Haupenthal Dr. Varsha R. Jumde Dr. M. Yagiz Ünver Prof. Dr. Andreas Heine Dr. Carlos Jamie Camacho Prof. Dr. Anna K. H. Hirsch Prof. Dr. Gerhard Klebe Prof. Dr. Alexander Dömling 《ChemMedChem》2020,15(8):680-684
Pharmacophore searches that include anchors, fragments contributing above average to receptor binding, combined with one-step syntheses are a powerful approach for the fast discovery of novel bioactive molecules. Here, we are presenting a pipeline for the rapid and efficient discovery of aspartyl protease inhibitors. First, we hypothesized that hydrazine could be a multi-valent warhead to interact with the active site Asp carboxylic acids. We incorporated the hydrazine anchor in a multicomponent reaction and created a large virtual library of hydrazine derivatives synthetically accessible in one-step. Next, we performed anchor-based pharmacophore screening of the libraries and resynthesized top-ranked compounds. The inhibitory potency of the molecules was finally assessed by an enzyme activity assay and the binding mode confirmed by several soaked crystal structures supporting the validity of the hypothesis and approach. The herein reported pipeline of tools will be of general value for the rapid generation of receptor binders beyond Asp proteases. 相似文献
143.
Davide Ciardiello Brigida Anna Maiorano Paola Parente Maria Grazia Rodriquenz Tiziana Pia Latiano Cinzia Chiarazzo Valerio Pazienza Luigi Pio Guerrera Brunella Amoruso Nicola Normanno Giulia Martini Fortunato Ciardiello Erika Martinelli Evaristo Maiello 《International journal of molecular sciences》2022,23(2)
Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response. 相似文献
144.
Anna Kloska Grzegorz M. Cech Dariusz Nowicki Monika Macig-Dorszyska Aleksandra E. Bogucka Stephanie Markert Drte Becher Katarzyna Potrykus Paulina Czaplewska Agnieszka Szalewska-Paasz 《International journal of molecular sciences》2022,23(2)
Osmotic changes are common challenges for marine microorganisms. Bacteria have developed numerous ways of dealing with this stress, including reprogramming of global cellular processes. However, specific molecular adaptation mechanisms to osmotic stress have mainly been investigated in terrestrial model bacteria. In this work, we aimed to elucidate the basis of adjustment to prolonged salinity challenges at the proteome level in marine bacteria. The objects of our studies were three representatives of bacteria inhabiting various marine environments, Shewanella baltica, Vibrio harveyi and Aliivibrio fischeri. The proteomic studies were performed with bacteria cultivated in increased and decreased salinity, followed by proteolytic digestion of samples which were then subjected to liquid chromatography with tandem mass spectrometry analysis. We show that bacteria adjust at all levels of their biological processes, from DNA topology through gene expression regulation and proteasome assembly, to transport and cellular metabolism. The finding that many similar adaptation strategies were observed for both low- and high-salinity conditions is particularly striking. The results show that adaptation to salinity challenge involves the accumulation of DNA-binding proteins and increased polyamine uptake. We hypothesize that their function is to coat and protect the nucleoid to counteract adverse changes in DNA topology due to ionic shifts. 相似文献
145.
Ewa Witkowska Magda Godlewska Jowita Osiejuk Sandra Gtarz Beata Wileska Katarzyna Kosiska Joanna Starnowska-Sok Anna Piotrowska Piotr F. J. Lipiski Joanna Mataliska Jolanta Dyniewicz Pawe K. Halik Ewa Gniazdowska Barbara Przewlocka Aleksandra Misicka 《International journal of molecular sciences》2022,23(2)
Based on the mechanism of neuropathic pain induction, a new type of bifunctional hybrid peptidomimetics was obtained for potential use in this type of pain. Hybrids consist of two types of pharmacophores that are connected by different types of linkers. The first pharmacophore is an opioid agonist, and the second pharmacophore is an antagonist of the pronociceptive system, i.e., an antagonist of the melanocortin-4 receptor. The results of tests in acute and neuropathic pain models of the obtained compounds have shown that the type of linker used to connect pharmacophores had an effect on antinociceptive activity. Peptidomimetics containing longer flexible linkers were very effective at low doses in the neuropathic pain model. To elucidate the effect of linker lengths, two hybrids showing very high activity and two hybrids with lower activity were further tested for affinity for opioid (mu, delta) and melanocortin-4 receptors. Their complexes with the target receptors were also studied by molecular modelling. Our results do not show a simple relationship between linker length and affinity for particular receptor types but suggest that activity in neuropathic pain is related to a proper balance of receptor affinity rather than maximum binding to any or all of the target receptors. 相似文献
146.
Herpes simplex virus types 1 and 2 HSV1 and 2, namely varicella-zoster VZV and cytomegalovirus CMV, are among the most common pathogens worldwide. They remain in the host body for life. The course of infection with these viruses is often asymptomatic or mild and self-limiting, but in immunocompromised patients, such as solid organ or bone marrow transplant recipients, the course can be very severe or even life-threatening. Unfortunately, in the latter group, the highest percentage of infections with strains resistant to routinely used drugs is observed. On the other hand, frequent recurrences of genital herpes can be a problem even in people with normal immunity. Genital herpes also increases the risk of acquiring sexually transmitted diseases, including HIV infection and, if present in pregnant women, poses a risk to the fetus and newborn. Even more frequently than herpes simplex, congenital infections can be caused by cytomegalovirus. We present the most important anti-herpesviral agents, the mechanisms of resistance to these drugs, and the associated mutations in the viral genome. Special emphasis was placed on newly introduced drugs such as maribavir and brincidofovir. We also briefly discuss the most promising substances in preclinical testing as well as immunotherapy options and vaccines currently in use and under investigation. 相似文献
147.
Claudia Zagami Diana Papp Alice Anna Daddi Francesco Boccellato 《International journal of molecular sciences》2022,23(7)
The adult gastric mucosa is characterised by deep invaginations of the epithelium called glands. These tissue architectural elements are maintained with the contribution of morphogen signals. Morphogens are expressed in specific areas of the tissue, and their diffusion generates gradients in the microenvironment. Cells at different positions in the gland sense a specific combination of signals that instruct them to differentiate, proliferate, regenerate, or migrate. Differentiated cells perform specific functions involved in digestion, such as the production of protective mucus and the secretion of digestive enzymes or gastric acid. Biopsies from gastric precancerous conditions usually display tissue aberrations and change the shape of the glands. Alteration of the morphogen signalling microenvironment is likely to underlie those conditions. Furthermore, genes involved in morphogen signalling pathways are found to be frequently mutated in gastric cancer. We summarise the most recent findings regarding alterations of morphogen signalling during gastric carcinogenesis, and we highlight the new stem cell technologies that are improving our understanding of the regulation of human tissue shape. 相似文献
148.
Joanna Kisaa Anna Tomaszewska Adriana Barylyak Yaroslav Bobitski Maciej Balawejder 《International journal of molecular sciences》2022,23(7)
Flame retardants have attracted growing environmental concern. Recently, an increasing number of studies have been conducted worldwide to investigate flame-retardant sources, environmental distribution, living organisms’ exposure, and toxicity. The presented studies include the degradation of 4,4′-isopropylidenebis(2,6-dibromophenol) (TBBPA) by ozonolysis and photocatalysis. In the photocatalytic process, nano- and micro-magnetite (n-Fe3O4 and μ-Fe3O4) are used as a catalyst. Monitoring of TBBPA decay in the photocatalysis and ozonolysis showed photocatalysis to be more effective. Significant removal of TBBPA was achieved within 10 min in photocatalysis (ca. 90%), while for ozonation, a comparable effect was observed within 70 min. To determine the best method of TBBPA degradation concentration on COD and TOC, the removals were examined. The highest oxidation state was obtained for photocatalysis on μ-Fe3O4, whereas for n-Fe3O4 and ozonolysis, the COD/TOC ratio was lower. Acute toxicity results show noticeable differences in the toxicity of TBBPA and its degradation products to Artemia franciscana and Thamnocephalus platyurus. The EC50 values indicate that TBBPA degradation products were toxic to harmful, whereas the TBPPA and post-reaction mixtures were toxic to the invertebrate species tested. The best efficiency in the removal and degradation of TBBPA was in the photocatalysis process on μ-Fe3O4 (reaction system 1). The examined crustaceans can be used as a sensitive test for acute toxicity evaluation. 相似文献
149.
Anna Sadakierska-Chudy Pawe Szymanowski Arleta Lebioda Rafa Poski 《International journal of molecular sciences》2022,23(7)
Rectal prolapse is influenced by many factors including connective tissue dysfunction. Currently, there is no data about genetic contribution in the etiology of this disorder. In this study, we performed trio whole-exome sequencing in an 11-year-old girl with mucosal rectal prolapse and her parents and sibling. Genetic testing revealed a novel heterozygous missense variant c.1406G>T; p.G469V in exon 11 of the COLGALT2 gene encoding the GLT25 D2 enzyme. Sanger sequencing confirmed this variant only in the patient while the mother, father and sister showed a wild-type sequence. The pathogenicity of the novel variant was predicted using 10 different in silico tools that classified it as pathogenic. Further, in silico prediction, according to Phyre2, Project HOPE, I-Mutant3.0 and MutPred2 showed that the missense variant can decrease protein stability and cause alterations in the physical properties of amino acids resulting in structural and functional changes of the GLT25D2 protein. In conclusion, the present study identifies a previously unknown missense mutation in the COLGALT2 gene that encodes the enzyme involved in collagen glycosylation. The clinical features observed in the patient and the results of in silico analysis suggest that the new genetic variant can be pathogenic. 相似文献
150.
Anna Vallverdú-Queralt José Fernando Rinaldi de Alvarenga Ramon Estruch Rosa M. Lamuela-Raventos 《Food chemistry》2013
Sofrito is a key component of the Mediterranean diet, a diet that is strongly associated with a reduced risk of cardiovascular events. In this study, different Mediterranean sofritos were analysed for their content of polyphenols and carotenoids after a suitable work-up extraction procedure using liquid chromatography/electrospray ionisation-linear ion trap quadrupole-Orbitrap-mass spectrometry (LC/ESI-LTQ-Orbitrap-MS) and liquid chromatography/electrospray ionisation tandem triple quadrupole mass spectrometry (LC/ESI-MS-MS). In this way, 40 polyphenols (simple phenolic and hydroxycinnamoylquinic acids, and flavone, flavonol and dihydrochalcone derivatives) were identified with very good mass accuracy (<2 mDa), and confirmed by accurate mass measurements in MS and MS2 modes. The high-resolution MS analyses revealed the presence of polyphenols never previously reported in Mediterranean sofrito. The quantification levels of phenolic and carotenoid compounds led to the distinction of features among different Mediterranean sofritos according to the type of vegetables (garlic and onions) or olive oil added for their production. 相似文献