全文获取类型
收费全文 | 1417篇 |
免费 | 155篇 |
国内免费 | 22篇 |
专业分类
综合类 | 52篇 |
化学工业 | 955篇 |
金属工艺 | 25篇 |
机械仪表 | 42篇 |
建筑科学 | 32篇 |
能源动力 | 2篇 |
轻工业 | 287篇 |
水利工程 | 4篇 |
石油天然气 | 5篇 |
无线电 | 54篇 |
一般工业技术 | 105篇 |
冶金工业 | 10篇 |
原子能技术 | 4篇 |
自动化技术 | 17篇 |
出版年
2024年 | 6篇 |
2023年 | 61篇 |
2022年 | 301篇 |
2021年 | 355篇 |
2020年 | 69篇 |
2019年 | 60篇 |
2018年 | 41篇 |
2017年 | 46篇 |
2016年 | 61篇 |
2015年 | 65篇 |
2014年 | 52篇 |
2013年 | 53篇 |
2012年 | 63篇 |
2011年 | 51篇 |
2010年 | 44篇 |
2009年 | 39篇 |
2008年 | 34篇 |
2007年 | 41篇 |
2006年 | 19篇 |
2005年 | 22篇 |
2004年 | 21篇 |
2003年 | 14篇 |
2002年 | 5篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1981年 | 1篇 |
1951年 | 1篇 |
排序方式: 共有1594条查询结果,搜索用时 15 毫秒
1.
Bilal Alashkar Alhamwe Daniel P. Potaczek Sarah Miethe Fahd Alhamdan Lukas Hintz Arslan Magomedov Holger Garn 《International journal of molecular sciences》2021,22(9)
Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma. 相似文献
2.
In vivo Kinetic Biodistribution of Nano‐Sized Outer Membrane Vesicles Derived from Bacteria
下载免费PDF全文
![点击此处可从《Small (Weinheim an der Bergstrasse, Germany)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Su Chul Jang Sae Rom Kim Yae Jin Yoon Kyong‐Su Park Ji Hyun Kim Jaewook Lee Oh Youn Kim Eun‐Jeong Choi Dae‐Kyum Kim Dong‐Sic Choi Yoon‐Keun Kim Jaesung Park Dolores Di Vizio Yong Song Gho 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(4):456-461
Evaluation of kinetic distribution and behaviors of nanoparticles in vivo provides crucial clues into their roles in living organisms. Extracellular vesicles are evolutionary conserved nanoparticles, known to play important biological functions in intercellular, inter‐species, and inter‐kingdom communication. In this study, the first kinetic analysis of the biodistribution of outer membrane vesicles (OMVs)—bacterial extracellular vesicles—with immune‐modulatory functions is performed. OMVs, injected intraperitoneally, spread to the whole mouse body and accumulate in the liver, lung, spleen, and kidney within 3 h of administration. As an early systemic inflammation response, increased levels of TNF‐α and IL‐6 are observed in serum and bronchoalveolar lavage fluid. In addition, the number of leukocytes and platelets in the blood is decreased. OMVs and cytokine concentrations, as well as body temperature are gradually decreased 6 h after OMV injection, in concomitance with the formation of eye exudates, and of an increase in ICAM‐1 levels in the lung. Following OMV elimination, most of the inflammatory signs are reverted, 12 h post‐injection. However, leukocytes in bronchoalveolar lavage fluid are increased as a late reaction. Taken together, these results suggest that OMVs are effective mediators of long distance communication in vivo. 相似文献
3.
Emma Layton Anna-Marie Fairhurst Sam Griffiths-Jones Richard K. Grencis Ian S. Roberts 《International journal of molecular sciences》2020,21(23)
In eukaryotes, microRNAs (miRNAs) have roles in development, homeostasis, disease and the immune response. Recent work has shown that plant and mammalian miRNAs also mediate cross-kingdom and cross-domain communications. However, these studies remain controversial and are lacking critical mechanistic explanations. Bacteria do not produce miRNAs themselves, and therefore it is unclear how these eukaryotic RNA molecules could function in the bacterial recipient. In this review, we compare and contrast the biogenesis and functions of regulatory RNAs in eukaryotes and bacteria. As a result, we discovered several conserved features and homologous components in these distinct pathways. These findings enabled us to propose novel mechanisms to explain how eukaryotic miRNAs could function in bacteria. Further understanding in this area is necessary to validate the findings of existing studies and could facilitate the use of miRNAs as novel tools for the directed remodelling of the human microbiota. 相似文献
4.
Sebastian Sjoqvist Kentaro Otake Yoshihiko Hirozane 《International journal of molecular sciences》2020,21(24)
There is a lack of reliable biomarkers for disorders of the central nervous system (CNS), and diagnostics still heavily rely on symptoms that are both subjective and difficult to quantify. The cerebrospinal fluid (CSF) is a promising source of biomarkers due to its close connection to the CNS. Extracellular vesicles are actively secreted by cells, and proteomic analysis of CSF extracellular vesicles (EVs) and their molecular composition likely reflects changes in the CNS to a higher extent compared with total CSF, especially in the case of neuroinflammation, which could increase blood–brain barrier permeability and cause an influx of plasma proteins into the CSF. We used proximity extension assay for proteomic analysis due to its high sensitivity. We believe that this methodology could be useful for de novo biomarker discovery for several CNS diseases. We compared four commercially available kits for EV isolation: MagCapture and ExoIntact (based on magnetic beads), EVSecond L70 (size-exclusion chromatography), and exoEasy (membrane affinity). The isolated EVs were characterized by nanoparticle tracking analysis, ELISA (CD63, CD81 and albumin), and proximity extension assay (PEA) using two different panels, each consisting of 92 markers. The exoEasy samples did not pass the built-in quality controls and were excluded from downstream analysis. The number of detectable proteins in the ExoIntact samples was considerably higher (~150% for the cardiovascular III panel and ~320% for the cell regulation panel) compared with other groups. ExoIntact also showed the highest intersample correlation with an average Pearson’s correlation coefficient of 0.991 compared with 0.985 and 0.927 for MagCapture and EVSecond, respectively. The median coefficient of variation was 5%, 8%, and 22% for ExoIntact, MagCapture, and EVSecond, respectively. Comparing total CSF and ExoIntact samples revealed 70 differentially expressed proteins in the cardiovascular III panel and 17 in the cell regulation panel. To our knowledge, this is the first time that CSF EVs were analyzed by PEA. In conclusion, analysis of CSF EVs by PEA is feasible, and different isolation kits give distinct results, with ExoIntact showing the highest number of identified proteins with the lowest variability. 相似文献
5.
Alessandro Lucidi Danilo Buca Carlo Ronsini Sara Tinari Giuseppina Bologna Davide Buca Martina Leombroni Marco Liberati Francesco DAntonio Giovanni Scambia Paola Lanuti Marco Petrillo 《International journal of molecular sciences》2020,21(22)
Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients. 相似文献
6.
7.
Tuntun Wang Dr. Sitansu Sekhar Nanda Dr. Georgia C. Papaefthymiou Prof. Dong Kee Yi 《Chembiochem : a European journal of chemical biology》2020,21(9):1254-1264
The extracellular matrix (ECM) is a macromolecular network that can provide biochemical and structural support for cell adhesion and formation. It regulates cell behavior by influencing biochemical and physical cues. It is a dynamic structure whose components are modified, degraded, or deposited during connective tissue development, giving tissues strength and structural integrity. The physical properties of the natural ECM environment control the design of naturally or synthetically derived biomaterials to guide cell function in tissue engineering. Tissue engineering is an important field that explores physical cues of the ECM to produce new viable tissue for medical applications, such as in organ transplant and organ recovery. Understanding how the ECM exerts physical effects on cell behavior, when cells are seeded in synthetic ECM scaffolds, is of utmost importance. Herein we review recent findings in this area that report on cell behaviors in a variety of ECMs with different physical properties, i.e., topology, geometry, dimensionality, stiffness, and tension. 相似文献
8.
Ana Rita Gomes Nasim Bahram Sangani Tiago G. Fernandes M. Margarida Diogo Leopold M. G. Curfs Chris P. Reutelingsperger 《International journal of molecular sciences》2020,21(24)
The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics. 相似文献
9.
Evangelos Pavlakis Michelle Neumann Thorsten Stiewe 《International journal of molecular sciences》2020,21(24)
Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination. 相似文献
10.
Scaffold‐guided tissue engineering based on synthetic and natural occurring polymers has gained many interests in recent year. In this study, the development of a chitosan‐heparin artificial extracellular matrix (AECM) is reported. Three‐dimensional, macroporous composite AECMs composed of heparin (Hep) and chitosan (Chito) were prepared by an interpolyelectrolyte complex/lyophilization method. The Chito‐Hep composite AECMs were, respectively, crosslinked with glutaraldehyde, as well as cocrosslinked with N,N‐(3‐dimethylaminopropyl)‐N′‐ethyl carbodiimide (EDC/NHS) and N‐hydroxysuccinimide (NHS). The crosslinking reactions were examined by FT‐IR analysis. In physiological buffer solution (PBS), the EDC/NHS‐crosslinked Chito‐Hep composite AECM showed a relative lower water retention ratio than its glutaraldehyde‐crosslinked counterparts. The EDC/NHS‐crosslinked Chito‐Hep composite AECMs showed excellent biocompatibility, according to the results of the in vitro cytotoxic test. This result suggested that the EDC/NHS‐crosslinked Chito‐Hep composite AECMs might be a potential biomaterial for scaffold‐guided tissue engineering applications. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 相似文献