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21.
Carolina Gismene Jorge Enrique Hernndez Gonzlez Angela Rocio Nio Santisteban Andrey Fabricio Ziem Nascimento Lucas dos Santos Cunha Fbio Rogrio de Moraes Cristiano Luis Pinto de Oliveira Caio C. Oliveira Paola Jocelan Scarin Provazzi Pedro Geraldo Pascutti Raghuvir Krishnaswamy Arni Ricardo Barros Mariutti 《International journal of molecular sciences》2022,23(17)
Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity. 相似文献
22.
Jessica Maiuolo Francesca Oppedisano Cristina Carresi Micaela Gliozzi Vincenzo Musolino Roberta Macrì Federica Scarano Annarita Coppoletta Antonio Cardamone Francesca Bosco Rocco Mollace Carolina Muscoli Ernesto Palma Vincenzo Mollace 《International journal of molecular sciences》2022,23(24)
Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as “nitrate tolerance”, which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2. 相似文献
23.
24.
João Luiz Pozzobon Taiane Missau Carolina Ceolin Druck Mutlu Özcan 《Journal of Adhesion Science and Technology》2016,30(4):412-421
This study evaluated the effect of air-abrasion parameters such as particle size, distance, and time on adhesion of resin cement to zirconium dioxide (Y-TZP) and t→m phase transformation. Y-TZP blocks (N = 80) (In-Ceram YZ, Vita) (4 mm3?×?4 mm3?×?3 mm3) were assigned into eight groups (n = 10): air-abrasion with 30 μm (CoJet Sand, S30) and 110 μm (Rocatec-Plus, S110) silica-coated alumina particles, applied for either for 10–20 s (T = time), from a distance of 10–20 mm (D = distance), composing the following groups: S30T10D10, S30T10D20, S30T20D10, S30T20D20, S110T10D10, S110T10D20, S110T20D10, and S110T20D20. Resin composite (RelyX ARC) was bonded to Y-TZP blocks in polyethylene molds. The specimens were aged (10,000 thermal cycles and water storage for 90 days) prior to shear bond test. Failure types were analyzed under stereomicroscope and SEM, and phase transformation was calculated. Data (MPa) were analyzed using 3-way ANOVA and Tukey’s tests. Air-abrasion with 110 μm silica particles (10.96) presented significantly higher bond strength (p = 0.0149) compared to 30 μm (8.96). Time (p = 0.403) and distance (p = 0.179) parameters did not affect the results significantly. Air-abrasion with 110 μm particles (12.3) promoted higher bond strength than that of 30 μm (6.4) when applied for 10 s from a distance of 10 mm (Tukey’s). Failure types were predominantly adhesive. Phase transformation ranged between 30.3 and 35.9% for 30 μm particles and 23.8–43.7% for 110 μm particles. While the size of silica-coated alumina particles were more relevant parameter for resin cement adhesion to Y-TZP, time (up to 20 s) and distance (up to 20 mm) appear to be less pertinent. 相似文献
25.
Riccardo Turchi Flavia Tortolici Monica Benvenuto Carolina Punziano Anastasia De Luca Stefano Rufini Raffaella Faraonio Roberto Bei Daniele Lettieri-Barbato Katia Aquilano 《International journal of molecular sciences》2023,24(1)
Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability. We used in vitro models of BC (MCF7 and MDA-MB-231) that were maintained with a low amount of sulfur amino acids (SAAs) and a high amount of oxidizable polyunsatured fatty acids (PUFAs). Treatment with anti-apoptotic, anti-ferroptotic and antioxidant drugs were used to determine the modality of cell death. We reproduced these conditions in vivo by feeding BC-bearing mice with a diet poor in proteins and SAAs and rich in PUFAs (LSAA/HPUFA). Western blot analysis, qPCR and histological analyses were used to assess the anti-cancer effects and the molecular pathways involved. We found that BC cells underwent oxidative damage to DNA and proteins and both apoptosis and ferroptosis were induced. Along with caspases-mediated PARP1 cleavage, we found a lowering of the GSH-GPX4 system and an increase of lipid peroxides. A LSAA/HPUFA diet reduced tumor mass and its vascularization and immune cell infiltration, and induced apoptosis and ferroptotic hallmarks. Furthermore, mitochondrial mass was found to be increased, and the buffering of mitochondrial reactive oxygen species limited GPX4 reduction and DNA damage. Our results suggest that administration of custom diets, targeting the dependency of cancer cells on certain nutrients, can represent a promising complementary option for anti-cancer therapy. 相似文献
26.
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
27.
Federico Perez Carolina Nayme Ruera Emanuel Miculan Paula Carasi Fernando Gabriel Chirdo 《International journal of molecular sciences》2021,22(14)
The small intestine has a high rate of cell turnover under homeostatic conditions, and this increases further in response to infection or damage. Epithelial cells mostly die by apoptosis, but recent studies indicate that this may also involve pro-inflammatory pathways of programmed cell death, such as pyroptosis and necroptosis. Celiac disease (CD), the most prevalent immune-based enteropathy, is caused by loss of oral tolerance to peptides derived from wheat, rye, and barley in genetically predisposed individuals. Although cytotoxic cells and gluten-specific CD4+ Th1 cells are the central players in the pathology, inflammatory pathways induced by cell death may participate in driving and sustaining the disease through the release of alarmins. In this review, we summarize the recent literature addressing the role of programmed cell death pathways in the small intestine, describing how these mechanisms may contribute to CD and discussing their potential implications. 相似文献
28.
Effect of surfactants and gelatin on the stability,rheology, and encapsulation efficiency of W1/O/W2 multiple emulsions containing avocado oil 下载免费PDF全文
29.
Sofía Valla Nourhan Hassan Daiana Lujn Vitale Daniela Madanes Fiorella Mercedes Spinelli Felipe C. O. B. Teixeira Burkhard Greve Nancy Adriana Espinoza-Snchez Carolina Cristina Laura Alaniz Martin Gtte 《International journal of molecular sciences》2021,22(11)
Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors. 相似文献
30.
The encapsulation of enterocins synthesized by Enterococcus faecium CRL1385 through ionic gelation with calcium ions was analyzed. Different enterocins samples were lyophilised and encapsulated using low-methoxyl pectin as the coating material. Lipids present in milk butter were also added to control the release of antimicrobial peptides from the capsules. The morphology of fresh and freeze-dried capsules was examined using light microscopy and scanning electron microscopy, respectively. Antimicrobial activity of encapsulated bacteriocins was assessed against Listeria monocytogenes 01/155 using the agar diffusion technique and direct contact in microplates. The capsules with higher lipid content showed a more spherical and uniform shape. Pathogen inhibition was observed for capsules prepared with different bacteriocin solutions both on solid (halo diameter = 8.5–13.5 mm) and in an aqueous medium (ca. 2 log orders decline in L. monocytogenes viability). The outcomes suggest that bacteriocin encapsulation through ionic gelation can be a potential alternative for the application of these antimicrobial peptides as biopreservatives in food. 相似文献