全文获取类型
收费全文 | 6419篇 |
免费 | 455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 | 2825篇 |
金属工艺 | 78篇 |
机械仪表 | 86篇 |
建筑科学 | 263篇 |
矿业工程 | 35篇 |
能源动力 | 160篇 |
轻工业 | 1130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 | 937篇 |
冶金工业 | 321篇 |
原子能技术 | 15篇 |
自动化技术 | 630篇 |
出版年
2024年 | 16篇 |
2023年 | 112篇 |
2022年 | 668篇 |
2021年 | 774篇 |
2020年 | 231篇 |
2019年 | 211篇 |
2018年 | 254篇 |
2017年 | 207篇 |
2016年 | 263篇 |
2015年 | 224篇 |
2014年 | 271篇 |
2013年 | 449篇 |
2012年 | 374篇 |
2011年 | 412篇 |
2010年 | 276篇 |
2009年 | 274篇 |
2008年 | 276篇 |
2007年 | 243篇 |
2006年 | 214篇 |
2005年 | 152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 | 35篇 |
1997年 | 42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 | 9篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1974年 | 4篇 |
1966年 | 5篇 |
排序方式: 共有6885条查询结果,搜索用时 15 毫秒
31.
Kinga Ciechanowska Maria Pokornowska Anna Kurzyska-Kokorniak 《International journal of molecular sciences》2021,22(2)
Ribonuclease Dicer belongs to the family of RNase III endoribonucleases, the enzymes that specifically hydrolyze phosphodiester bonds found in double-stranded regions of RNAs. Dicer enzymes are mostly known for their essential role in the biogenesis of small regulatory RNAs. A typical Dicer-type RNase consists of a helicase domain, a domain of unknown function (DUF283), a PAZ (Piwi-Argonaute-Zwille) domain, two RNase III domains, and a double-stranded RNA binding domain; however, the domain composition of Dicers varies among species. Dicer and its homologues developed only in eukaryotes; nevertheless, the two enzymatic domains of Dicer, helicase and RNase III, display high sequence similarity to their prokaryotic orthologs. Evolutionary studies indicate that a combination of the helicase and RNase III domains in a single protein is a eukaryotic signature and is supposed to be one of the critical events that triggered the consolidation of the eukaryotic RNA interference. In this review, we provide the genetic insight into the domain organization and structure of Dicer proteins found in vertebrate and invertebrate animals, plants and fungi. We also discuss, in the context of the individual domains, domain deletion variants and partner proteins, a variety of Dicers’ functions not only related to small RNA biogenesis pathways. 相似文献
32.
Karolina Bukowska-Strakova Joanna Wodek Ewelina Pitera Magdalena Kozakowska Anna Konturek-Ciela Maciej Ciela Monika Goka Witold Nowak Aleksandra Wieczorek Katarzyna Pawiska-Wsikowska Alicja Jzkowicz Maciej Siedlar 《International journal of molecular sciences》2021,22(3)
Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(−413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients. 相似文献
33.
Roberto Lande Immacolata Pietraforte Anna Mennella Raffaella Palazzo Francesca Romana Spinelli Konstantinos Giannakakis Francesca Spadaro Mario Falchi Valeria Riccieri Katia Stefanantoni Curdin Conrad Cristiano Alessandri Fabrizio Conti Loredana Frasca 《International journal of molecular sciences》2021,22(4)
LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers. 相似文献
34.
Amir Mohammadzadeh Pter P. Lakatos Mihly Balogh Ferenc Zdor Dvid rpd Kardi Zoltn S. Zdori Kornl Kirly Anna Rita Galambos Szilvia Barsi Pl Riba Sndor Benyhe Lszl Kles Tams Tbi va Szk Laszlo G. Harsing Jr. Mahmoud Al-Khrasani 《International journal of molecular sciences》2021,22(5)
The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP. 相似文献
35.
Anna Iwaniak Damir Mogut Piotr Minkiewicz Justyna ulewska Magorzata Darewicz 《International journal of molecular sciences》2021,22(6)
In silico and in vitro methods were used to analyze ACE- and DPP-IV-inhibiting potential of Gouda cheese with a modified content of β-casein. Firstly, the BIOPEP-UWM database was used to predict the presence of ACE and DPP-IV inhibitors in casein sequences. Then, the following Gouda cheeses were produced: with decreased, increased, and normative content of β-casein after 1 and 60 days of ripening each (six variants in total). Finally, determination of the ACE/DPP-IV-inhibitory activity and the identification of peptides in respective Gouda-derived water-soluble extracts were carried out. The identification analyses were supported with in silico calculations, i.e., heatmaps and quantitative parameters. All Gouda variants exhibited comparable ACE inhibition, whereas DPP-IV inhibition was more diversified among the samples. The samples derived from Gouda with the increased content of β-casein (both stages of ripening) had the highest DPP-IV-inhibiting potency compared to the same samples measured for ACE inhibition. Regardless of the results concerning ACE and DPP-IV inhibition among the cheese samples, the heatmap showed that the latter bioactivity was predominant in all Gouda variants, presumably because it was based on the qualitative approach (i.e., peptide presence in the sample). Our heatmap did not include the bioactivity of a single peptide as well as its quantity in the sample. In turn, the quantitative parameters showed that the best sources of ACE/DPP-IV inhibitors were all Gouda-derived extracts obtained after 60 days of the ripening. Although our protocol was efficient in showing some regularities among Gouda cheese variants, in vivo studies are recommended for more extensive investigations of this subject. 相似文献
36.
Katarzyna Romanowska-Prchnicka Anna Felis-Giemza Marzena Olesiska Piotr Wojdasiewicz Agnieszka Paradowska-Gorycka Dariusz Szukiewicz 《International journal of molecular sciences》2021,22(6)
Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered. 相似文献
37.
新版房间空调器的能效标准GB 21455-2019《房间空气调节器能效限定值及能效等级》中将定频热泵型房间空调器能效等级评价指标调整为全年能源消耗效率APF值,为了提高检测质量,评定APF的不确定度显得尤为重要.通过空气焓值法对空调器性能进行测试,对APF的计算、测量以及不确定度的评估等进行了分析,得到APF的相对扩展不确定度为1.96%,其中额定制冷量引入的不确定度分量最大,占比达75.11%.以额定制冷工况为例,对额定制冷量影响较大的测量参数为室内侧进风湿球温度和室内侧出风湿球温度,不确定度分量占比分别达51.99%和36.42%. 相似文献
38.
Kavitej Samra Mathun Kuganesan William Smith Anna Kleyman Robert Tidswell Nishkantha Arulkumaran Mervyn Singer Alex Dyson 《International journal of molecular sciences》2021,22(6)
Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe−/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H2O2), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed. 相似文献
39.
40.
Katarzyna Kili-Pstrusiska Anna Wiela-Hojeska 《International journal of molecular sciences》2021,22(8)
Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases. 相似文献