全文获取类型
收费全文 | 733篇 |
免费 | 81篇 |
国内免费 | 1篇 |
学科分类
工业技术 | 815篇 |
出版年
2024年 | 1篇 |
2023年 | 9篇 |
2022年 | 6篇 |
2021年 | 156篇 |
2020年 | 47篇 |
2019年 | 40篇 |
2018年 | 35篇 |
2017年 | 34篇 |
2016年 | 47篇 |
2015年 | 32篇 |
2014年 | 37篇 |
2013年 | 56篇 |
2012年 | 51篇 |
2011年 | 59篇 |
2010年 | 32篇 |
2009年 | 24篇 |
2008年 | 24篇 |
2007年 | 25篇 |
2006年 | 19篇 |
2005年 | 9篇 |
2004年 | 12篇 |
2003年 | 10篇 |
2002年 | 8篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 5篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1976年 | 1篇 |
排序方式: 共有815条查询结果,搜索用时 15 毫秒
11.
Aleksandra Nijak Johan Saenen Alain J. Labro Dorien Schepers Bart L. Loeys Maaike Alaerts 《International journal of molecular sciences》2021,22(6)
Brugada syndrome (BrS) is an inherited cardiac arrhythmia that predisposes to ventricular fibrillation and sudden cardiac death. It originates from oligogenic alterations that affect cardiac ion channels or their accessory proteins. The main hurdle for the study of the functional effects of those variants is the need for a specific model that mimics the complex environment of human cardiomyocytes. Traditionally, animal models or transient heterologous expression systems are applied for electrophysiological investigations, each of these models having their limitations. The ability to create induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), providing a source of human patient-specific cells, offers new opportunities in the field of cardiac disease modelling. Contemporary iPSC-CMs constitute the best possible in vitro model to study complex cardiac arrhythmia syndromes such as BrS. To date, thirteen reports on iPSC-CM models for BrS have been published and with this review we provide an overview of the current findings, with a focus on the electrophysiological parameters. We also discuss the methods that are used for cell derivation and data acquisition. In the end, we critically evaluate the knowledge gained by the use of these iPSC-CM models and discuss challenges and future perspectives for iPSC-CMs in the study of BrS and other arrhythmias. 相似文献
12.
Anita Romanowska Katarzyna Wgrzyn Katarzyna Bury Emilia Sikorska Aleksandra Gnatek Agnieszka Piwkowska Igor Konieczny Adam Lesner Magdalena Wysocka 《International journal of molecular sciences》2021,22(5)
The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)n-O2Oc-NH2, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]8-O2Oc-NH2 and typical for large proteins. 相似文献
13.
14.
Marta Krychowiak-Manicka Mirosawa Krauze-Baranowska Sylwia Godlewska Zbigniew Kaczyski Aleksandra Bielicka-Giedo Natalia Grzegorczyk Magdalena Narajczyk Joanna E. Frackowiak Aleksandra Krolicka 《International journal of molecular sciences》2021,22(9)
Carnivorous plants are exemplary natural sources of secondary metabolites with biological activity. However, the therapeutic antimicrobial potential of these compounds is limited due to intrinsic resistance of selected bacterial pathogens, among which Pseudomonas aeruginosa represents an extreme example. The objective of the study was to overcome the intrinsic resistance of P. aeruginosa by combining silver nanoparticles (AgNPs) with secondary metabolites from selected carnivorous plant species. We employed the broth microdilution method, the checkerboard titration technique and comprehensive phytochemical analyses to define interactions between nanoparticles and active compounds from carnivorous plants. It has been confirmed that P. aeruginosa is resistant to a broad range of secondary metabolites from carnivorous plants, i.e., naphthoquinones, flavonoids, phenolic acids (MBC = 512 µg mL−1) and only weakly sensitive to their mixtures, i.e., extracts and extracts’ fractions. However, it was shown that the antimicrobial activity of extracts and fractions with a significant level of naphthoquinone (plumbagin) was significantly enhanced by AgNPs. Our studies clearly demonstrated a crucial role of naphthoquinones in AgNPs and extract interaction, as well as depicted the potential of AgNPs to restore the bactericidal activity of naphthoquinones towards P. aeruginosa. Our findings indicate the significant potential of nanoparticles to modulate the activity of selected secondary metabolites and revisit their antimicrobial potential towards human pathogenic bacteria. 相似文献
15.
Justyna Korczynska Aleksandra Czumaj Michal Chmielewski Julian Swierczynski Tomasz Sledzinski 《International journal of molecular sciences》2021,22(9)
Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk. 相似文献
16.
Aleksandra A. Ageeva Ilya M. Magin Alexander B. Doktorov Victor F. Plyusnin Polina S. Kuznetsova Alexander A. Stepanov Alexander A. Alekseev Nikolay E. Polyakov Tatyana V. Leshina 《International journal of molecular sciences》2021,22(12)
The study of the L- and D-amino acid properties in proteins and peptides has attracted considerable attention in recent years, as the replacement of even one L-amino acid by its D-analogue due to aging of the body is resulted in a number of pathological conditions, including Alzheimer’s and Parkinson’s diseases. A recent trend is using short model systems to study the peculiarities of proteins with D-amino acids. In this report, the comparison of the excited states quenching of L- and D-tryptophan (Trp) in a model donor–acceptor dyad with (R)- and (S)-ketoprofen (KP-Trp) was carried out by photochemically induced dynamic nuclear polarization (CIDNP) and fluorescence spectroscopy. Quenching of the Trp excited states, which occurs via two mechanisms: prevailing resonance energy transfer (RET) and electron transfer (ET), indeed demonstrates some peculiarities for all three studied configurations of the dyad: (R,S)-, (S,R)-, and (S,S)-. Thus, the ET efficiency is identical for (S,R)- and (R,S)-enantiomers, while RET differs by 1.6 times. For (S,S)-, the CIDNP coefficient is almost an order of magnitude greater than for (R,S)- and (S,R)-. To understand the source of this difference, hyperpolarization of (S,S)-and (R,S)- has been calculated using theory involving the electron dipole–dipole interaction in the secular equation. 相似文献
17.
18.
Jolanta Koliska Aleksandra Grzelakowska Jolanta Sokoowska 《Coloration Technology》2019,135(6):501-509
The sensing properties of dyes based on 2(1H) quinolones containing dicyanoethylene groups towards selected anions such as CN?, F?, I?, Cl?, SCN?, CH3COO?, and were evaluated. The spectroscopic responses of these compounds were investigated in a solution of acetonitrile/water (1:9, v/v) and phosphate buffer at a pH of 7.4. These dyes were found to act as efficient colorimetric and high turn–off fluorescent sensors to cyanide anions. The fluorescence intensity was linearly related to the concentration of CN? from 1 to 10 µmol/L, and the detection limits reached a micromolar level of 6.7, 11.1, 3.8 and 7.2 µmol/L for 1‐4 , respectively. The cytotoxic effect of the dyes against human neuroblastoma cells (SH‐SY5Y) was also determined by MTT assay. The examined compounds exhibited slight cytotoxicity against cells under experimental conditions. 相似文献
19.
Lorenc-Kubis I Kowalska J Pochroń B Zuzło A Wilusz T 《Chembiochem : a European journal of chemical biology》2001,2(1):45-51
LUTI (Linum usitatissimum trypsin inhibitor), a member of the potato inhibitor I family, has been isolated from seeds of flax by ethanol fractionation, ion exchange chromatography on CM-Sephadex C-25, affinity purification on immobilized methylchymotrypsin (alpha-chymotrypsin in which His57 has been converted to 3-methylhistidine) in the presence of 5M NaCl, and finally by reversed-phase HPLC. The 7655 Da inhibitor consists of a single polypeptide chain of 69 residues with one disulfide bridge. The molecule is acetylated at the N terminus. Its primary structure has been determined after limited proteolysis of the native molecule with trypsin at the reactive site, cleavage with cyanogen bromide or arginyl endopeptidase (Arg-gingipain), and alcoholytic deacetylation of the N-terminally blocked serine. The association constants (K(a)) of LUTI with bovine beta-trypsin and alpha-chymotrypsin are 3.58x10(10) M(-1) and 5.02x10(5) M(-1), respectively. High NaCl concentration (3M) increased the association constant of LUTI with alpha-chymotrypsin to 6.64x10(7) M(-1). To our knowledge, LUTI is the first serine-proteinase-type inhibitor isolated from a plant of the Linaceae family. 相似文献
20.
This paper presents the results of studies of wall effects in commercial soap-based greases LT4-S2 and HUTPLEX EP-2, thickened with, respectively, lithium 12-hydroxystearate and overbased calcium sulfonate. The studies were conducted in the presence of five different materials: copper alloy C11000, bronze B476, EPDM rubber and PTFE and PU thermoplastics. The influence of the energy state of the surface layer of the adsorbents and temperature (ranging from ?20 to 60 °C) on the intensity of wall effects was investigated. Changes in the structural viscosity and shear stress in the boundary layer area in the greases and the soap-based thickener’s ability to adsorb on the surfaces of the adsorbents were determined by evaluating the rheological parameter plateau modulus. 相似文献