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21.
Marie-Christine Lebart Franoise Trousse Gilles Valette Joan Torrent Morgane Denus Nadine Mestre-Frances Anne Marcilhac 《International journal of molecular sciences》2022,23(15)
Reg-1α/lithostathine, a protein mainly associated with the digestive system, was previously shown to be overexpressed in the pre-clinical stages of Alzheimer’s disease. In vitro, the glycosylated protein was reported to form fibrils at physiological pH following the proteolytic action of trypsin. However, the nature of the protease able to act in the central nervous system is unknown. In the present study, we showed that Reg-1α can be cleaved in vitro by calpain-2, the calcium activated neutral protease, overexpressed in neurodegenerative diseases. Using chemical crosslinking experiments, we found that the two proteins can interact with each other. Identification of the cleavage site using mass spectrometry, between Gln4 and Thr5, was found in agreement with the in silico prediction of the calpain cleavage site, in a position different from the one reported for trypsin, i.e., Arg11-Ile12 peptide bond. We showed that the cleavage was impeded by the presence of the neighboring glycosylation of Thr5. Moreover, in vitro studies using electron microscopy showed that calpain-cleaved protein does not form fibrils as observed after trypsin cleavage. Collectively, our results show that calpain-2 cleaves Reg-1α in vitro, and that this action is not associated with fibril formation. 相似文献
22.
Sebastian Kummer Susanne Rinn Gunnar Seemann Nadine Bachmann Katherine Timothy Paul S. Thornton Frank Pillekamp Ertan Mayatepek Carsten Bergmann Thomas Meissner Niels Decher 《International journal of molecular sciences》2022,23(15)
The voltage-dependent L-type calcium channel isoform CaV1.2 is critically involved in many physiological processes, e.g., in cardiac action potential formation, electromechanical coupling and regulation of insulin secretion by beta cells. Gain-of-function mutations in the calcium voltage-gated channel subunit alpha 1 C (CACNA1C) gene, encoding the CaV1.2 α1-subunit, cause Timothy syndrome (TS), a multisystemic disorder that includes autism spectrum disorders and long QT (LQT) syndrome. Strikingly, TS patients frequently suffer from hypoglycemia of yet unproven origin. Using next-generation sequencing, we identified a novel heterozygous CACNA1C mutation in a patient with congenital hyperinsulinism (CHI) and associated hypoglycemic episodes. We characterized the electrophysiological phenotype of the mutated channel using voltage-clamp recordings and in silico action potential modeling experiments. The identified CaV1.2L566P mutation causes a mixed electrophysiological phenotype of gain- and loss-of-function effects. In silico action potential modeling supports that this mixed electrophysiological phenotype leads to a tissue-specific impact on beta cells compared to cardiomyocytes. Thus, CACNA1C variants may be associated with non-syndromic hyperinsulinemic hypoglycemia without long-QT syndrome, explained by very specific electrophysiological properties of the mutated channel. We discuss different biochemical characteristics and clinical impacts of hypoglycemia in the context of CACNA1C variants and show that these may be associated with significant morbidity for Timothy Syndrome patients. Our findings underline that the potential of hypoglycemia warrants careful attention in patients with CACNA1C variants, and such variants should be included in the differential diagnosis of non-syndromic congenital hyperinsulinism. 相似文献
23.
Initial Molecular Recognition Steps of McjA Precursor during Microcin J25 Lasso Peptide Maturation 下载免费PDF全文
Dr. Nadine Assrir Dr. Anna Pavelkova Régine Dazzoni Dr. Rémi Ducasse Dr. Nelly Morellet Dr. Eric Guittet Prof. Sylvie Rebuffat Dr. Séverine Zirah Dr. Yanyan Li Dr. Ewen Lescop 《Chembiochem : a European journal of chemical biology》2016,17(19):1851-1858
Microcin J25 (MccJ25) has emerged as an excellent model to understand the maturation of ribosomal precursor peptides into the entangled lasso fold. MccJ25 biosynthesis relies on the post‐translational modification of the precursor McjA by the ATP‐dependent protease McjB and the lactam synthetase McjC. Here, using NMR spectroscopy, we showed that McjA is an intrinsically disordered protein without detectable conformational preference, which emphasizes the active role of the maturation machinery on the three‐dimensional folding of MccJ25. We further showed that the N‐terminal region of the leader peptide is involved in interaction with both maturation enzymes and identified a predominant interaction of V43–S55 in the core McjA sequence with McjC. Moreover, we demonstrated that residues K23–Q34 in the N‐terminal McjA leader peptide tend to adopt a helical conformation in the presence of membrane mimics, implying a role in directing McjA to the membrane in the vicinity of the lasso synthetase/export machinery. These data provide valuable insights into the initial molecular recognition steps in the MccJ25 maturation process. 相似文献
24.
Mapesa JO Waldschmitt N Schmoeller I Blume C Hofmann T Mahungu S Clavel T Haller D 《Molecular nutrition & food research》2011,55(12):1850-1861
25.
Acidic cesium salts Csx
H3-xPW12O40 have been prepared by grinding together amounts of H3PW12O40 and porous Cs3PW12O40 compounds in varying stoichiometries. It is shown that this procedure leads to a dispersion of the acid on top of the high
surface area Cs3PW12O40 salt (160 m2 g-1), and, subsequently, yields high surface area materials which exhibit a much higher catalytic activity for n-butane isomerisation at 473 K when compared with samples prepared directly by chemical precipitation. This improvement holds
particularly true with low Cs content (x < 2).
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
26.
Long‐term testing of a high temperature polymer electrolyte membrane fuel cell: The effect of reactant gases 下载免费PDF全文
F. Javier Pinar Nadine Pilinski Peter Wagner 《American Institute of Chemical Engineers》2016,62(1):217-227
The investigations have been conducted with different oxidants and fuels with the aim of determining the state‐of‐the‐art of commercially available high temperature polymer electrolyte fuel cells based on polybenzimidazole for its application in combined heat and power generation systems. The fuel cell test performed with synthetic reformate (?63 μV/h) showed an increase of anode charge and mass transfer resistances. This behavior has suggested that CO may be generated from the CO2 included in the synthetic reformate via reverse water gas shift reaction. The fuel cell test performed with pure O2 developed the highest degradation rates (?70 μV/h) due to fast oxidative degradation of membrane electrode assembly materials such as cathode catalyst and membrane. Fuel cell operation with H2/air exhibited the lowest degradation rates (?57 μV/h) and it requires longer investigating times to identify the different degradation mechanisms. Moreover, fuel cell tests performed with air suggested longer break‐in procedures to complete catalyst activation and redistribution of electrolyte. © 2015 American Institute of Chemical Engineers AIChE J, 62: 217–227, 2016 相似文献
27.
Raffael Ott Xenia Pawlow Andreas Weiß Anna Hofelich Melanie Herbst Nadine Hummel Cornelia Prehn Jerzy Adamski Werner Rmisch-Margl Gabi Kastenmüller Anette-G. Ziegler Sandra Hummel 《International journal of molecular sciences》2020,21(24)
Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies. 相似文献
28.
Caroline Fauquant Valérie Briard‐Bion Nadine Leconte Michel Guichardant Marie‐Caroline Michalski 《European Journal of Lipid Science and Technology》2007,109(12):1167-1173
Native milk fat globules of various mean diameters, ranging from d43 = 2.3 µm to 8.0 µm, were obtained using microfiltration of raw whole milk. After milk fat globule washing, the milk fat globule membrane (MFGM) was separated by manual churning. After total lipid extraction and separation of polar lipids, their phospholipid (PL) and sterol composition was measured using thin‐layer chromatography, methyl ester analyses by gas chromatography, and gas chromatography coupled to mass spectrometry. The main PL species were phosphatidylethanolamine, phosphatidylcholine and sphingomyelin. The respective fatty acid composition of each PL species was measured. Many different minor bioactive sterols were detected in the MFGM, e.g. lanosterol, lathosterol, desmosterol, stigmasterol and β‐sitosterol. No significant differences in the PL and sterol profile were found between MFGM extracted from small and large milk fat globule fractions. 相似文献
29.
Nadine Reichhart Vladimir M. Milenkovic Christian H. Wetzel Olaf Strauß 《International journal of molecular sciences》2021,22(5)
The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4. 相似文献
30.
Monika Bednarczyk Carolina Medina-Montano Frederic Julien Fittler Henner Stege Meike Roskamp Michael Kuske Christian Langer Marco Vahldieck Evelyn Montermann Ingrid Tubbe Nadine Rhrig Andrzej Dzionek Stephan Grabbe Matthias Bros 《International journal of molecular sciences》2021,22(6)
The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses. 相似文献