全文获取类型
收费全文 | 3818篇 |
免费 | 203篇 |
国内免费 | 9篇 |
专业分类
电工技术 | 55篇 |
综合类 | 2篇 |
化学工业 | 1065篇 |
金属工艺 | 55篇 |
机械仪表 | 93篇 |
建筑科学 | 194篇 |
矿业工程 | 3篇 |
能源动力 | 155篇 |
轻工业 | 565篇 |
水利工程 | 43篇 |
石油天然气 | 43篇 |
无线电 | 267篇 |
一般工业技术 | 533篇 |
冶金工业 | 160篇 |
原子能技术 | 14篇 |
自动化技术 | 783篇 |
出版年
2024年 | 11篇 |
2023年 | 45篇 |
2022年 | 116篇 |
2021年 | 171篇 |
2020年 | 103篇 |
2019年 | 137篇 |
2018年 | 144篇 |
2017年 | 118篇 |
2016年 | 187篇 |
2015年 | 90篇 |
2014年 | 168篇 |
2013年 | 322篇 |
2012年 | 257篇 |
2011年 | 320篇 |
2010年 | 236篇 |
2009年 | 249篇 |
2008年 | 220篇 |
2007年 | 171篇 |
2006年 | 125篇 |
2005年 | 93篇 |
2004年 | 99篇 |
2003年 | 75篇 |
2002年 | 81篇 |
2001年 | 47篇 |
2000年 | 34篇 |
1999年 | 43篇 |
1998年 | 44篇 |
1997年 | 46篇 |
1996年 | 31篇 |
1995年 | 33篇 |
1994年 | 28篇 |
1993年 | 19篇 |
1992年 | 26篇 |
1991年 | 14篇 |
1990年 | 15篇 |
1989年 | 16篇 |
1988年 | 18篇 |
1987年 | 8篇 |
1986年 | 5篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 8篇 |
1982年 | 3篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1962年 | 1篇 |
排序方式: 共有4030条查询结果,搜索用时 15 毫秒
91.
Afshin Moradi Harsh Sharma Ravi Datta Sharma Achala Fernando Roberto A. Barrero Jyotsna Batra 《International journal of molecular sciences》2022,23(20)
Single nucleotide polymorphisms (SNPs) impacting the alternative splicing (AS) process (sQTLs) or isoform expression (iso-eQTL) are implicated as important cancer regulatory elements. To find the sQTL and iso-eQTL, we retrieved prostate cancer (PrCa) tissue RNA-seq and genotype data originating from 385 PrCa European patients from The Cancer Genome Atlas. We conducted RNA-seq analysis with isoform-based and splice event-based approaches. The MatrixEQTL was used to identify PrCa-associated sQTLs and iso-eQTLs. The overlap between sQTL and iso-eQTL with GWAS loci and those that are differentially expressed between cancer and normal tissue were identified. The cis-acting associations (FDR < 0.05) for PrCa-risk SNPs identified 42, 123, and 90 PrCa-associated cassette exons, intron retention, and mRNA isoforms belonging to 25, 95, and 83 genes, respectively; while assessment of trans-acting association (FDR < 0.05) yielded 59, 65, and 196 PrCa-associated cassette exons, intron retention and mRNA isoforms belonging to 35, 55, and 181 genes, respectively. The results suggest that functional PrCa-associated SNPs can play a role in PrCa genesis by making an important contribution to the dysregulation of AS and, consequently, impacting the expression of the mRNA isoforms. 相似文献
92.
Fernando Bonet Sabrina Brito Aez Jos Manuel Incio Matthias E. Futschik Jos Antonio Belo 《International journal of molecular sciences》2022,23(20)
The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the epicardium is a source of secreted growth factors that promote myocardial growth. CCBE1 is a secreted extracellular matrix protein expressed by epicardial cells that is required for the formation of the primitive coronary plexus. However, the role of CCBE1 during epicardial development was still unknown. Here, using a Ccbe1 knockout (KO) mouse model, we observed that loss of CCBE1 leads to congenital heart defects including thinner and hyper-trabeculated ventricular myocardium. In addition, Ccbe1 mutant hearts displayed reduced proliferation of cardiomyocyte and epicardial cells. Epicardial outgrowth culture assay to assess epicardial-derived cells (EPDC) migration showed reduced invasion of the collagen gel by EPDCs in Ccbe1 KO epicardial explants. Ccbe1 KO hearts also displayed fewer nonmyocyte/nonendothelial cells intramyocardially with a reduced proliferation rate. Additionally, RNA-seq data and experimental validation by qRT-PCR showed a marked deregulation of EMT-related genes in developing Ccbe1 mutant hearts. Together, these findings indicate that the myocardium defects in Ccbe1 KO mice arise from disruption of epicardial development and function. 相似文献
93.
Tamara Camino Nerea Lago-Baameiro Aurelio Sueiro Susana Beln Bravo Ivn Couto Francisco Fernando Santos Javier Baltar Felipe F. Casanueva María Pardo 《International journal of molecular sciences》2022,23(18)
Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague–Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity. 相似文献
94.
Lucas Bayons María Jos Guerra-Fernndez Fernando Hinostroza Ximena Bez-Matus Jacqueline Vsquez-Navarrete Luciana I. Gallo Sergio Parra Agustín D. Martínez Arlek Gonzlez-Jamett Fernando D. Marengo Ana M. Crdenas 《International journal of molecular sciences》2022,23(18)
Gain-of-function mutations of dynamin-2, a mechano-GTPase that remodels membrane and actin filaments, cause centronuclear myopathy (CNM), a congenital disease that mainly affects skeletal muscle tissue. Among these mutations, the variants p.A618T and p.S619L lead to a gain of function and cause a severe neonatal phenotype. By using total internal reflection fluorescence microscopy (TIRFM) in immortalized human myoblasts expressing the pH-sensitive fluorescent protein (pHluorin) fused to the insulin-responsive aminopeptidase IRAP as a reporter of the GLUT4 vesicle trafficking, we measured single pHluorin signals to investigate how p.A618T and p.S619L mutations influence exocytosis. We show here that both dynamin-2 mutations significantly reduced the number and durations of pHluorin signals induced by 10 μM ionomycin, indicating that in addition to impairing exocytosis, they also affect the fusion pore dynamics. These mutations also disrupt the formation of actin filaments, a process that reportedly favors exocytosis. This altered exocytosis might importantly disturb the plasmalemma expression of functional proteins such as the glucose transporter GLUT4 in skeletal muscle cells, impacting the physiology of the skeletal muscle tissue and contributing to the CNM disease. 相似文献
95.
Marina Paiva Abuafy Regina Celia Galvao Frem Giulia Polinario Fernando Rogerio Pavan Heng Zhao Angelika Mielcarek Cedric Boissiere Christian Serre Leila Aparecida Chiavacci 《International journal of molecular sciences》2022,23(14)
Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment. 相似文献
96.
Dr Fernando Leal 《AI & Society》1995,9(1):29-42
This paper first illustrates what kind of ethical issues arise from the new information, communication and automation technology. It then argues that we may embrace the popular idea that technology is ethically neutral or even ambivalent without having to close our eyes to those issues and in fact, that the ethical neutrality of technology makes them all the more urgent. Finally, it suggests that the widely ignored fact of normal responsible behaviour offers a new and fruitful starting point for any future thinking about such issues. 相似文献
97.
Jimena Leyria Samiha Benrabaa Marcela Nouzova Fernando G. Noriega Lilian Valadares Tose Francisco Fernandez-Lima Ian Orchard Angela B. Lange 《International journal of molecular sciences》2023,24(1)
The rigorous balance of endocrine signals that control insect reproductive physiology is crucial for the success of egg production. Rhodnius prolixus, a blood-feeding insect and main vector of Chagas disease, has been used over the last century as a model to unravel aspects of insect metabolism and physiology. Our recent work has shown that nutrition, insulin signaling, and two main types of insect lipophilic hormones, juvenile hormone (JH) and ecdysteroids, are essential for successful reproduction in R. prolixus; however, the interplay behind these endocrine signals has not been established. We used a combination of hormone treatments, gene expression analyses, hormone measurements, and ex vivo experiments using the corpus allatum or the ovary, to investigate how the interaction of these endocrine signals might define the hormone environment for egg production. The results show that after a blood meal, circulating JH levels increase, a process mainly driven through insulin and allatoregulatory neuropeptides. In turn, JH feeds back to provide some control over its own biosynthesis by regulating the expression of critical biosynthetic enzymes in the corpus allatum. Interestingly, insulin also stimulates the synthesis and release of ecdysteroids from the ovary. This study highlights the complex network of endocrine signals that, together, coordinate a successful reproductive cycle. 相似文献
98.
Vinicius Ruan Neves dos Santos Maria Karolina Martins Ferreira Leonardo Oliveira Bittencourt Paulo Fernando Santos Mendes Deiweson Souza-Monteiro Karolyny Martins Balbinot Joo de Jesus Viana Pinheiro Senda Charone Juliano Pelim Pessan Rafael Rodrigues Lima 《International journal of molecular sciences》2022,23(13)
There is currently a controversial and heated debate about the safety and ethical aspects of fluoride (F) used for human consumption. Thus, this study assessed the effects of prenatal and postnatal F exposure of rats on the salivary glands of their offspring. Pregnant rats were exposed to 0, 10, or 50 mg F/L from the drinking water, from the first day of gestation until offspring weaning (42 days). The offspring rats were euthanized for the collection of the parotid (PA) and submandibular (SM) glands, to assess the oxidative biochemistry and to perform morphometric and immunohistochemical analyses. F exposure was associated with a decrease in the antioxidant competence of PA in the 10 mg F/L group, contrasting with the increase observed in the 50 mg F/L group. On the other hand, the antioxidant competence of the SM glands was decreased at both concentrations. Moreover, both 10 and 50 mg F/L groups showed lower anti-α-smooth muscle actin immunostaining area in SM, while exposure to 50 mg F/L was associated with changes in gland morphometry by increasing the duct area in both glands. These findings demonstrate a greater susceptibility of the SM glands of the offspring to F at high concentration in comparison to PA, reinforcing the need to adhere to the optimum F levels recommended by the regulatory agencies. Such findings must be interpreted with caution, especially considering their translational meaning. 相似文献
99.
Gabriel Alves Bonaf Jssica Silva dos Santos Jussara Vaz Ziegler Fernando Augusto Lima Marson Thalita Rocha Manoela Marques Ortega 《International journal of molecular sciences》2022,23(13)
Glycyrrhizic acid (GA), a natural compound isolated from licorice (Glycyrrhiza glabra), has exhibited anti-inflammatory and anti-tumor effects in vitro. Dipotassium glycyrrhizinate (DPG), a dipotassium salt of GA, also has shown an anti-tumor effect on glioblastoma cell lines, U87MG and T98G. The study investigated the DPG effects in the melanoma cell line (SK-MEL-28). MTT assay demonstrated that the viability of the cells was significantly decreased in a time- and dose-dependent manner after DPG (IC50 = 36 mM; 24 h). DNA fragmentation suggested that DPG (IC50) induced cellular apoptosis, which was confirmed by a significant number of TUNEL-positive cells (p-value = 0.048) and by PARP-1 [0.55 vs. 1.02 arbitrary units (AUs), p-value = 0.001], BAX (1.91 vs. 1.05 AUs, p-value = 0.09), and BCL-2 (0.51 vs. 1.07 AUs, p-value = 0.0018) mRNA compared to control cells. The proliferation and wound-healing assays showed an anti-proliferative effect on DPG-IC50-treated cells, also indicating an inhibitory effect on cell migration (p-values < 0.001). Moreover, it was observed that DPG promoted a 100% reduction in melanospheres formation (p-value = 0.008). Our previous microRNAs (miRs) global analysis has revealed that DPG might increase miR-4443 and miR-3620 expression levels. Thus, qPCR showed that after DPG treatment, SK-MEL-28 cells presented significantly high miR-4443 (1.77 vs. 1.04 AUs, p-value = 0.02) and miR-3620 (2.30 vs. 1.00 AUs, p-value = 0.01) expression compared to control cells, which are predicted to target the NF-kB, CD209 and TNC genes, respectively. Both genes are responsible for cell attachment and migration, and qPCR revealed significantly decreased CD209 (1.01 vs. 0.54 AUs, p-value = 0.018) and TNC (1.00 vs. 0.31 AUs, p-value = 2.38 × 10−6) mRNA expression levels after DPG compared to untreated cells. Furthermore, the migration of SK-MEL-28 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) was attenuated by adding DPG by wound-healing assay (48 h: p-value = 0.004; 72 h: p-value = 7.0 × 10−4). In addition, the MMP-9 expression level was inhibited by DPG in melanoma cells stimulated by TPA and compared to TPA-treated cells (3.56 vs. 0.99 AUs, p-value = 0.0016) after 24 h of treatment. Our results suggested that DPG has an apoptotic, anti-proliferative, and anti-migratory effect on SK-MEL-28 cells. DPG was also able to inhibit cancer stem-like cells that may cause cerebral tumor formation. 相似文献
100.