全文获取类型
收费全文 | 3215篇 |
免费 | 209篇 |
国内免费 | 3篇 |
专业分类
电工技术 | 31篇 |
综合类 | 13篇 |
化学工业 | 1135篇 |
金属工艺 | 56篇 |
机械仪表 | 37篇 |
建筑科学 | 122篇 |
矿业工程 | 8篇 |
能源动力 | 73篇 |
轻工业 | 461篇 |
水利工程 | 32篇 |
石油天然气 | 14篇 |
无线电 | 150篇 |
一般工业技术 | 516篇 |
冶金工业 | 392篇 |
原子能技术 | 4篇 |
自动化技术 | 383篇 |
出版年
2023年 | 58篇 |
2022年 | 201篇 |
2021年 | 248篇 |
2020年 | 111篇 |
2019年 | 99篇 |
2018年 | 127篇 |
2017年 | 94篇 |
2016年 | 123篇 |
2015年 | 116篇 |
2014年 | 127篇 |
2013年 | 220篇 |
2012年 | 184篇 |
2011年 | 260篇 |
2010年 | 148篇 |
2009年 | 146篇 |
2008年 | 145篇 |
2007年 | 141篇 |
2006年 | 128篇 |
2005年 | 114篇 |
2004年 | 101篇 |
2003年 | 58篇 |
2002年 | 69篇 |
2001年 | 31篇 |
2000年 | 43篇 |
1999年 | 20篇 |
1998年 | 21篇 |
1997年 | 21篇 |
1996年 | 29篇 |
1995年 | 25篇 |
1994年 | 26篇 |
1993年 | 24篇 |
1992年 | 18篇 |
1991年 | 7篇 |
1990年 | 18篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 13篇 |
1986年 | 11篇 |
1985年 | 11篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1981年 | 8篇 |
1980年 | 3篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 8篇 |
1975年 | 6篇 |
1968年 | 3篇 |
1964年 | 2篇 |
排序方式: 共有3427条查询结果,搜索用时 15 毫秒
71.
Bin Qiu Susan E. Luczak Tamara L. Wall Aaron M. Kirchhoff Yuxue Xu Mimy Y. Eng Robert B. Stewart Weinian Shou Stephen L. Boehm II Julia A. Chester Weidong Yong Tiebing Liang 《International journal of molecular sciences》2016,17(8)
FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans. 相似文献
72.
Ultrastructure of the digestive tract in neotropical carnivorous catfish Hemisorubim platyrhynchos (Valenciennes, 1840) (Siluriformes,Pimelodidae) 下载免费PDF全文
73.
Kirk A. J. Stephenson Julia Zhu Adrian Dockery Laura Whelan Toms Burke Jacqueline Turner James J. OByrne G. Jane Farrar David J. Keegan 《International journal of molecular sciences》2022,23(2)
Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70–80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner. 相似文献
74.
Several surface treatments, using both commercially available coupling agents and reagents containing multiple amines, were applied to commingled continuous as-received AS4 carbon reinforcing fiber/liquid crystal polymer (LCP) matrix fibers. Unidirectional composites (normally 60 vol% carbon fiber) were prepared from as-received and treated commingled fibers and characterized. To estimate the effect the effect of the treatments on fiber-matrix adhesion, short beam shear (SBS) tests were conducted, the failure surfaces were examined, and spectroscopic studies wee performed. The mean SBS strength of the as-received unidirectional AS4 carbon fiber/LCP matrix composite system was 49 MPa. The best coupling agent and amine treatments yielded increases in composite shear strength of ∼ 10 to 20%, relative to the as-received AS4/LCP system. For the amine treatments, ESCA and FTIR analyses suggested of both the carbon and LCP fibers may have caused the increased adhesion. Moreover, SEM analysis of the failure surfaces of SBS specimens from composites prepared with the treated fibers may have caused the increased adhesion. Moreover, SEM analysis of the failure surfaces of SBS specimens from composites prepared with the treated fibers (both with coupling agents and amines) showed that strong fiber-matrix adhesion was present. That is, failure occurred in the LCP matrix material. 相似文献
75.
Gabriela Loscalzo Julia Scheel Jos Santiago Ibaez-Cabellos Eva García-Lopez Shailendra Gupta Jos Luis García-Gimenez Salvador Mena-Moll Alfredo Perales-Marín Jos Morales-Rosell 《International journal of molecular sciences》2022,23(1)
In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease. 相似文献
76.
Eva Harlacher Julia Wollenhaupt Constance C. F. M. J. Baaten Heidi Noels 《International journal of molecular sciences》2022,23(1)
Patients with chronic kidney disease (CKD) are at a highly increased risk of cardiovascular complications, with increased vascular inflammation, accelerated atherogenesis and enhanced thrombotic risk. Considering the central role of the endothelium in protecting from atherogenesis and thrombosis, as well as its cardioprotective role in regulating vasorelaxation, this study aimed to systematically integrate literature on CKD-associated endothelial dysfunction, including the underlying molecular mechanisms, into a comprehensive overview. Therefore, we conducted a systematic review of literature describing uremic serum or uremic toxin-induced vascular dysfunction with a special focus on the endothelium. This revealed 39 studies analyzing the effects of uremic serum or the uremic toxins indoxyl sulfate, cyanate, modified LDL, the advanced glycation end products N-carboxymethyl-lysine and N-carboxyethyl-lysine, p-cresol and p-cresyl sulfate, phosphate, uric acid and asymmetric dimethylarginine. Most studies described an increase in inflammation, oxidative stress, leukocyte migration and adhesion, cell death and a thrombotic phenotype upon uremic conditions or uremic toxin treatment of endothelial cells. Cellular signaling pathways that were frequently activated included the ROS, MAPK/NF-κB, the Aryl-Hydrocarbon-Receptor and RAGE pathways. Overall, this review provides detailed insights into pathophysiological and molecular mechanisms underlying endothelial dysfunction in CKD. Targeting these pathways may provide new therapeutic strategies reducing increased the cardiovascular risk in CKD. 相似文献
77.
Alessia Mariano Irene Bigioni Anna Scotto dAbusco Alessia Baseggio Conrado Simonetta Maina Antonio Francioso Luciana Mosca Mario Fontana 《International journal of molecular sciences》2022,23(1)
Pheomelanin is a natural yellow-reddish sulfur-containing pigment derived from tyrosinase-catalyzed oxidation of tyrosine in presence of cysteine. Generally, the formation of melanin pigments is a protective response against the damaging effects of UV radiation in skin. However, pheomelanin, like other photosensitizing substances, can trigger, following exposure to UV radiation, photochemical reactions capable of modifying and damaging cellular components. The photoproperties of this natural pigment have been studied by analyzing pheomelanin effect on oxidation/nitration of tyrosine induced by UVB radiation at different pH values and in presence of iron ions. Photoproperties of pheomelanin can be modulated by various experimental conditions, ranging from the photoprotection to the triggering of potentially damaging photochemical reactions. The study of the photomodification of l-Tyrosine in the presence of the natural pigment pheomelanin has a special relevance, since this tyrosine oxidation/nitration pathway can potentially occur in vivo in tissues exposed to sunlight and play a role in the mechanisms of tissue damage induced by UV radiation. 相似文献
78.
Alexander Balatskiy Ilia Ozhimalov Maria Balatskaya Alexandra Savina Julia Filatova Natalia Kalinina Vladimir Popov Vsevolod Tkachuk 《International journal of molecular sciences》2022,23(3)
The local development of atherosclerotic lesions may, at least partly, be associated with the specific cellular composition of atherosclerosis-prone regions. Previously, it was demonstrated that a small population of immature vascular smooth muscle cells (VSMCs) expressing both CD146 and neuron-glial antigen 2 is postnatally sustained in atherosclerosis-prone sites. We supposed that these cells may be involved in atherogenesis and can continuously respond to angiotensin II, which is an atherogenic factor. Using immunohistochemistry, flow cytometry, wound migration assay xCELLigence system, and calcium imaging, we studied the functional activities of immature VSMCs in vitro and in vivo. According to our data, these cells do not express nestin, CD105, and the leptin receptor. They are localized in atherosclerosis-prone regions, and their number increases with age, from 5.7% to 23%. Immature VSMCs do not migrate to low shear stress areas and atherosclerotic lesions. They also do not have any unique response to angiotensin II. Thus, despite the localization of immature VSMCs and the presence of the link between their number and age, our study did not support the hypothesis that immature VSMCs are directly involved in the formation of atherosclerotic lesions. Additional lineage tracing studies can clarify the fate of these cells during atherogenesis. 相似文献
79.
Juan Carlos Fernndez-Martín Ana María Espinosa-Oliva Irene García-Domínguez Isaac Rosado-Snchez Yolanda M. Pacheco Rosario Moyano Jos G. Monterde Jos Luis Venero Rocío M. de Pablos 《International journal of molecular sciences》2022,23(3)
Lipopolysaccharide (LPS)-induced endotoxemia induces an acute systemic inflammatory response that mimics some important features of sepsis, the disease with the highest mortality rate worldwide. In this work, we have analyzed a murine model of endotoxemia based on a single intraperitoneal injection of 5 mg/kg of LPS. We took advantage of galectin-3 (Gal3) knockout mice and found that the absence of Gal3 decreased the mortality rate oflethal endotoxemia in the first 80 h after the administration of LPS, along with a reduction in the tissular damage in several organs measured by electron microscopy. Using flow cytometry, we demonstrated that, in control conditions, peripheral immune cells, especially monocytes, exhibited high levels of Gal3, which were early depleted in response to LPS injection, thus suggesting Gal3 release under endotoxemia conditions. However, serum levels of Gal3 early decreased in response to LPS challenge (1 h), an indication that Gal3 may be extravasated to peripheral organs. Indeed, analysis of Gal3 in peripheral organs revealed a robust up-regulation of Gal3 36 h after LPS injection. Taken together, these results demonstrate the important role that Gal3 could play in the development of systemic inflammation, a well-established feature of sepsis, thus opening new and promising therapeutic options for these harmful conditions. 相似文献
80.
Amalia Ruiz-Serrano Christina N. Boyle Josep M. Monn Rodríguez Julia Günter Agnieszka E. Jucht Svende Pfundstein Andreas M. Bapst Thomas A. Lutz Roland H. Wenger Carsten C. Scholz 《International journal of molecular sciences》2022,23(3)
Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis. 相似文献