全文获取类型
| 收费全文 | 748篇 |
| 免费 | 11篇 |
专业分类
| 电工技术 | 7篇 |
| 化学工业 | 238篇 |
| 金属工艺 | 12篇 |
| 机械仪表 | 14篇 |
| 建筑科学 | 34篇 |
| 能源动力 | 17篇 |
| 轻工业 | 114篇 |
| 水利工程 | 7篇 |
| 石油天然气 | 2篇 |
| 无线电 | 81篇 |
| 一般工业技术 | 100篇 |
| 冶金工业 | 59篇 |
| 原子能技术 | 3篇 |
| 自动化技术 | 71篇 |
出版年
| 2024年 | 15篇 |
| 2023年 | 9篇 |
| 2022年 | 61篇 |
| 2021年 | 60篇 |
| 2020年 | 28篇 |
| 2019年 | 25篇 |
| 2018年 | 26篇 |
| 2017年 | 27篇 |
| 2016年 | 27篇 |
| 2015年 | 11篇 |
| 2014年 | 29篇 |
| 2013年 | 46篇 |
| 2012年 | 43篇 |
| 2011年 | 46篇 |
| 2010年 | 32篇 |
| 2009年 | 27篇 |
| 2008年 | 22篇 |
| 2007年 | 27篇 |
| 2006年 | 14篇 |
| 2005年 | 7篇 |
| 2004年 | 21篇 |
| 2003年 | 7篇 |
| 2002年 | 7篇 |
| 2001年 | 5篇 |
| 2000年 | 8篇 |
| 1999年 | 7篇 |
| 1998年 | 23篇 |
| 1997年 | 15篇 |
| 1996年 | 12篇 |
| 1995年 | 6篇 |
| 1994年 | 9篇 |
| 1993年 | 6篇 |
| 1992年 | 5篇 |
| 1991年 | 3篇 |
| 1990年 | 4篇 |
| 1989年 | 1篇 |
| 1988年 | 3篇 |
| 1987年 | 4篇 |
| 1986年 | 2篇 |
| 1985年 | 6篇 |
| 1984年 | 5篇 |
| 1983年 | 1篇 |
| 1982年 | 3篇 |
| 1981年 | 3篇 |
| 1980年 | 2篇 |
| 1979年 | 1篇 |
| 1977年 | 3篇 |
| 1976年 | 3篇 |
| 1975年 | 1篇 |
| 1924年 | 1篇 |
排序方式： 共有759条查询结果，搜索用时 15 毫秒
591.
Maria N. Starodubtseva Sofia Karachrysafi Nastassia M. Shkliarava Irina A. Chelnokova Dimitrios Kavvadas Kyriaki Papadopoulou Paraskevi Samara Vasileios Papaliagkas Antonia Sioga Anastasia Komnenou Vasileios Karampatakis Theodora Papamitsou 《International journal of molecular sciences》2022,23(18)
Background: Fungal infections can pose great threat to sight. Immediate treatment is usually required; antifungal agents are widely accepted and are effective in most cases. The present experimental study aims to investigate the probable effects of intravitreal injection of antifungal agents on the structure and mechanical properties of the surface of peripheral blood erythrocytes. Methods: Nine albino New Zealand white rabbits, aged five months old, were chosen for the experiment. Solutions of micafungin, voriconazole, or balanced salt solution (BSS) were injected into the midvitreous. Animals were divided into two experimental groups and one control group. Blood sampling from an intravenous (IV) line was performed after 10 days from the last IV injection. An atomic force microscope (AFM) was used to study the structural and mechanical properties of cell surfaces. Results: The analysis results showed that the parameters of the cytoskeleton’s spatial organization changed insignificantly with the antifungal drug treatment. Conclusions: Our findings suggest that locally administered antifungal drugs can cause significant changes to the structure and frictional properties of the erythrocyte surface. These effects occur in the long-term period after administration of the drugs and represent a potential possibility for violation of blood supply to tissues, and the further development of negative side effects. 相似文献
592.
Fbio Trindade Antnio S. Barros Jssica Silva Antonia Vlahou Inês Falco-Pires Sofia Guedes Carla Vitorino Rita Ferreira Adelino Leite-Moreira Francisco Amado Rui Vitorino 《International journal of molecular sciences》2021,22(11)
Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine. 相似文献
593.
Olga A. Averina Ivan G. Laptev Mariia A. Emelianova Oleg A. Permyakov Sofia S. Mariasina Alyona I. Nikiforova Vasily N. Manskikh Olga O. Grigorieva Anastasia K. Bolikhova Gennady A. Kalabin Olga A. Dontsova Petr V. Sergiev 《International journal of molecular sciences》2022,23(11)
Mitochondrial translation is a unique relic of the symbiotic origin of the organelle. Alterations of its components cause a number of severe human diseases. Hereby we report a study of mice devoid of Mettl15 mitochondrial 12S rRNA methyltransferase, responsible for the formation of m4C839 residue (human numbering). Homozygous Mettl15−/− mice appeared to be viable in contrast to other mitochondrial rRNA methyltransferase knockouts reported earlier. The phenotype of Mettl15−/− mice is much milder than that of other mutants of mitochondrial translation apparatus. In agreement with the results obtained earlier for cell cultures with an inactivated Mettl15 gene, we observed accumulation of the RbfA factor, normally associated with the precursor of the 28S subunit, in the 55S mitochondrial ribosome fraction of knockout mice. A lack of Mettl15 leads to a lower blood glucose level after physical exercise relative to that of the wild-type mice. Mettl15−/− mice demonstrated suboptimal muscle performance and lower levels of Cox3 protein synthesized by mitoribosomes in the oxidative soleus muscles. Additionally, we detected decreased learning capabilities in the Mettl15−/− knockout mice in the tests with both positive and negative reinforcement. Such properties make Mettl15−/− knockout mice a suitable model for mild mitochondriopathies. 相似文献
594.
Sofia Raftopoulou Paulina Valadez-Cosmes Zala Nikita Mihalic Rudolf Schicho Julia Kargl 《International journal of molecular sciences》2022,23(6)
Neutrophils are immune cells with reported phenotypic and functional plasticity. Tumor-associated neutrophils display many roles during cancer progression. Several tumor microenvironment (TME)-derived factors orchestrate neutrophil release from the bone marrow, recruitment and functional polarization, while simultaneously neutrophils are active stimulators of the TME by secreting factors that affect immune interactions and subsequently tumor progression. Successful immunotherapies for many cancer types and stages depend on the targeting of tumor-infiltrating lymphocytes. Neutrophils impact the success of immunotherapies, such as immune checkpoint blockade therapies, by displaying lymphocyte suppressive properties. The identification and characterization of distinct neutrophil subpopulations or polarization states with pro- and antitumor phenotypes and the identification of the major TME-derived factors of neutrophil polarization would allow us to harness the full potential of neutrophils as complementary targets in anticancer precision therapies. 相似文献
595.
Paolo Rosa Sofia Scibetta Giuseppe Pepe Giorgio Mangino Luca Capocci Sam J. Moons Thomas J. Boltje Francesco Fazi Vincenzo Petrozza Alba Di Pardo Vittorio Maglione Antonella Calogero 《International journal of molecular sciences》2022,23(17)
Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, and radio- and chemoresistance, that have direct impacts on treatment failure. Thus, there is still an increasing need to identify novel targets to limit GBM relapse. Polysialic acid (PSA) is a carbohydrate composed of a linear polymer of α2,8-linked sialic acids, primarily attached to the Neural Cell Adhesion Molecule (NCAM). It is considered an oncodevelopmental antigen that is re-expressed in various tumors. High levels of PSA-NCAM are associated with high-grade and poorly differentiated tumors. Here, we investigated the effect of PSA inhibition in GBM cells under low oxygen concentrations. Our main results highlight the way in which hypoxia stimulates polysialylation in U87-MG cells and in a GBM primary culture. By lowering PSA levels with the sialic acid analog, F-NANA, we also inhibited GBM cell migration and interfered with their differentiation influenced by the hypoxic microenvironment. Our findings suggest that PSA may represent a possible molecular target for the development of alternative pharmacological strategies to manage a devastating tumor like GBM. 相似文献
596.
Tatiana Maurício Susana Aveiro Sofia Guedes Diana Lopes Tnia Melo Bruno M. Neves Rosrio Domingues Pedro Domingues 《International journal of molecular sciences》2022,23(4)
In recent years, several studies have demonstrated that polyunsaturated fatty acids have strong immunomodulatory properties, altering several functions of macrophages. In the present work, we sought to provide a multi-omic approach combining the analysis of the lipidome, the proteome, and the metabolome of RAW 264.7 macrophages supplemented with phospholipids containing omega-3 (PC 18:0/22:6; ω3-PC) or omega-6 (PC 18:0/20:4; ω6-PC) fatty acids, alone and in the presence of lipopolysaccharide (LPS). Supplementation of macrophages with ω3 and ω6 phospholipids plus LPS produced a significant reprogramming of the proteome of macrophages and amplified the immune response; it also promoted the expression of anti-inflammatory proteins (e.g., pleckstrin). Supplementation with the ω3-PC and ω6-PC induced significant changes in the lipidome, with a marked increase in lipid species linked to the inflammatory response, attributed to several pro-inflammatory signalling pathways (e.g., LPCs) but also to the pro-resolving effect of inflammation (e.g., PIs). Finally, the metabolomic analysis demonstrated that supplementation with ω3-PC and ω6-PC induced the expression of several metabolites with a pronounced inflammatory and anti-inflammatory effect (e.g., succinate). Overall, our data show that supplementation of macrophages with ω3-PC and ω6-PC effectively modulates the lipidome, proteome, and metabolome of these immune cells, affecting several metabolic pathways involved in the immune response that are triggered by inflammation. 相似文献
597.
Andrey Giovanni Gomes de Oliveira Mikhail V. Dubovichenko Ahmed A. ElDeeb Joseph Wanjohi Sofia Zablotskaya Dr. Dmitry M. Kolpashchikov 《Chembiochem : a European journal of chemical biology》2021,22(10):1750-1754
Oligonucleotide gene therapy (OGT) agents suppress specific mRNAs in cells and thus reduce the expression of targeted genes. The ability to unambiguously distinguish cancer from healthy cells can solve the low selectivity problem of OGT agents. Cancer RNA markers are expressed in both healthy and cancer cells with a higher expression level in cancer cells. We have designed a DNA-based construct, named DNA thresholder (DTh) that cleaves targeted RNA only at high concentrations of cancer marker RNA and demonstrates low cleavage activity at low marker concentrations. The RNA-cleaving activity can be adjusted within one order of magnitude of the cancer marker RNA concentration by simply redesigning DTh. Importantly, DTh recognizes cancer marker RNA, while cleaving targeted RNA; this offers a possibility to suppress vital genes exclusively in cancer cells, thus triggering their death. DTh is a prototype of computation-inspired molecular device for controlling gene expression and cancer treatment. 相似文献
598.
Mariana Ferreira-Duarte Tiago Rodrigues-Pinto Teresa Sousa Miguel A. Faria Maria Sofia Rocha Daniela Menezes-Pinto Marisa Esteves-Monteiro Fernando Magro Patrícia Dias-Pereira Margarida Duarte-Araújo Manuela Morato 《International journal of molecular sciences》2021,22(9)
Angiotensin II (Ang II) regulates colon contraction, acting not only directly on smooth muscle but also indirectly, interfering with myenteric neuromodulation mediated by the activation of AT1 /AT2 receptors. In this article, we aimed to explore which mediators and cells were involved in Ang II-mediated colonic contraction in the TNBS-induced rat model of colitis. The contractile responses to Ang II were evaluated in distinct regions of the colon of control animals or animals with colitis in the absence and presence of different antagonists/inhibitors. Endogenous levels of Ang II in the colon were assessed by ELISA and the number of AT1/AT2 receptors by qPCR. Ang II caused AT1 receptor-mediated colonic contraction that was markedly decreased along the colons of TNBS-induced rats, consistent with reduced AT1 mRNA expression. However, the effect mediated by Ang II is much more intricate, involving (in addition to smooth muscle cells and nerve terminals) ICC and EGC, which communicate by releasing ACh and NO in a complex mechanism that changes colitis, unveiling new therapeutic targets. 相似文献
599.
E Br?ndle R Hautmann P Alken A Hesse R Sch?fer M Richter-Reichhelm K Schalkh?user H Huland H Rübben H Melchior 《Canadian Metallurgical Quarterly》1997,36(6):585-587
Serial single photon emission computed tomography (SPECT), near-infrared spectroscopy (NIRS), and transcranial doppler (TCD) sonography examinations were performed to investigate changes of cerebral perfusion and tissue oxygenation in a patient with complicated cerebral malaria that have been acquired in Nigeria. On admission to the Neurologic Intensive Care Unit in Innsbruck, Austria, SPECT and NIRS revealed focal right hemispheric hypoperfusion and decreased oxygen saturation, respectively, correlating exactly to the patient's right hemispheric localizing signs. In contrast, TCD examinations of the basal cerebral vessels revealed normal flow patterns. The patient showed an initial Plasmodium falciparum parasitemia rate of 30% and was cured by intravenous quinine and oral mefloquine therapy. He was discharged without neurologic symptoms. Follow-up SPECT and NIRS examinations revealed regular cerebral perfusion and oxygenation patterns in both cortical hemispheres. In summary, the presented findings provide first evidence that noninvasive SPECT and NIRS may be important diagnostic tools in the evaluation of impaired cerebral microcirculation in patients with P. falciparum malaria. 相似文献
600.
Tim?WaltonEmail authorView author&#;s OrcID profile Michael?Evans David?Kirk Frank?Melchior 《Personal and Ubiquitous Computing》2018,22(4):707-720
Mobile devices enable users to consume media with audio content in a wide range of contexts, with environmental noise being present in many of these. Several methods exist that aim to improve the experience of mobile listening by utilising information about the environmental noise, such as volume and dynamic range adaptation. This paper explores a fundamentally different approach to improving the mobile listening experience by using the object-based audio paradigm, where individual audio sources are mixed in response to each specific listening context. Three experimental studies, containing both quantitative and qualitative aspects, are presented which investigate whether environmental noise influences preference of background-foreground audio object balance in a mix. The results indicate that environmental noise can influence the preferred audio mix and that the nature of the adaptations made is dependent upon both audio content and user. Additionally, qualitative analysis provides an understanding of the role of environmental noise on preferred audio mix. It is believed that the content adaptation method explored in this paper is a simple yet useful tool for adapting content to suit both the context and the user. 相似文献