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111.
Amitesh Maiti William L. Shaw Samantha M. Clarke Christie Fox Lucia A. Ke William N. Cheung Mark A. Burton Graham D. Kosiba Christian D. Grant Richard H. Gee 《Propellants, Explosives, Pyrotechnics》2024,49(2):e202300253
While most performance metrics of high-explosive (HE) based devices like detonation velocity, detonation pressure, and energy output are expected to degrade over time, the evolution of initiation threshold appears less clear, with claims of both increasing and decreasing trends in threshold having been made in the literature. This work analyzes D-optimally designed sequential binary test data for a few thermally conditioned porous-powder and polymer-bonded HE initiator systems using a Bayesian likelihood method employing the probit regression model. We find that in most cases the initiation threshold decreases (i. e., sensitivity increases) upon accelerated thermal conditioning. However, such results are nuanced and influenced by factors like the contact area of initiating stimulus, HE characteristics like density and specific surface area, as well as possible thermally induced changes to other materials and interfaces involved. 相似文献
112.
113.
Angelo Lucia Peter A. DiMaggio Meghan L. Bellows Leah M. Octavio 《Computers & Chemical Engineering》2005,29(11-12):2363
Normal alkanes show very complicated phase transition kinetics and macroscopic phase equilibrium behavior. This paper focuses on the phase stability and equilibrium of complicated mixtures like n-alkanes and on the enabling global optimization technologies needed to gather problem knowledge. The new ideas contained in this paper include:
- (1) novel level set methods for gathering encoded knowledge;
- (2) the differential geometry for uncovering pathways to more subtle knowledge;
- (3) all supporting non-linearly constrained optimization techniques;
- (4) all data handling needed to unravel complex solution structure.
114.
Evelyn M. Templeton Moritz Lass Torsten Kleffmann Leigh J. Ellmers Suetonia C. Palmer Trent Davidson Nicola J. A. Scott John W. Pickering Christopher J. Charles Zoltan H. Endre Vicky A. Cameron A. Mark Richards Miriam T. Rademaker Anna P. Pilbrow 《International journal of molecular sciences》2022,23(2)
One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)—an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra–mass spectrometry (SWATH–MS) in kidney cortices from control sheep (n = 5), sheep with established rapid-pacing-induced ADHF (n = 8), and sheep after ~4 weeks recovery from ADHF (n = 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2–2.6-fold, adjusted p < 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted p < 0.01) and acute phase response (repressed during recovery from ADHF; adjusted p < 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients. 相似文献
115.
Maria Lucia Iacovino Chiara Carmen Miceli Marco De Felice Biagio Barone Luca Pompella Francesco Chiancone Erika Di Zazzo Giuseppe Tirino Carminia Maria Della Corte Ciro Imbimbo Ferdinando De Vita Felice Crocetto 《International journal of molecular sciences》2022,23(3)
Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification. 相似文献
116.
11C‐ and 18F‐Labeled Radioligands for P‐Glycoprotein Imaging by Positron Emission Tomography 下载免费PDF全文
Dr. Mariangela Cantore Marcel Benadiba Philip H. Elsinga Chantal Kwizera Rudi A. J. O. Dierckx Nicola Antonio Colabufo Gert Luurtsema 《ChemMedChem》2016,11(1):108-118
P‐Glycoprotein (P‐gp) is an efflux transporter widely expressed at the human blood–brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P‐gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2‐[2‐(2‐methyl‐(11C)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline ([11C]‐ 5 ); 2‐[2‐(2‐fluoromethyl‐(18F)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetra‐hydroisoquinoline ([18F]‐ 6 ); and 2‐[2‐(2‐fluoroethyl‐(18F)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline ([18F]‐ 7 ), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P‐gp. Methyl derivative [11C]‐ 5 is a potent P‐gp substrate, whereas the corresponding fluoroethyl derivative [18F]‐ 7 is a P‐gp inhibitor. Fluoromethyl compound [18F]‐ 6 is classified as a non‐transported P‐gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [11C]‐ 5 and [18F]‐ 7 , respectively, for in vivo imaging of P‐gp by using PET. 相似文献
117.
Lucia Marsich Alessio Ferluga Norman Venturini Marco Caniato Orfeo Sbaizero Chiara Schmid 《Polymer Engineering and Science》2016,56(7):727-734
In the field of self‐reinforced composites many researchers have focused their attention on the coextruded tapes composed of polypropylene core and PP/PE copolymer skin. Two similar commercial fabrics (P and T) have been compared in respect of their peel resistance. For both materials, peel resistance has a periodic trend that regularly follows fabric weave style. T has demonstrated an average peel resistance and a well‐bonded area slightly greater than P. Skin/core interfacial properties have been investigated and a crosscheck between differential scanning calorimetry (DSC) and Raman spectroscopy has been adopted to understand the influence of skin structure on consolidated laminate. DSC curves exhibit three melting peaks during first heating for both fabrics, corresponding to copolymer, skin/core interface, and core melting. After consolidation at 140°C stretching‐induced superstructure and PP crystallinity degree are preserved. The presence of PP/PE copolymer + PE blend only in fabric P has been pointed out and PE content has been calculated. POLYM. ENG. SCI., 56:727–734, 2016. © 2016 Society of Plastics Engineers 相似文献
118.
Lydia Francis Decheng Meng Ian C Locke Jonathan C Knowles Nicola Mordan Vehid Salih Aldo R Boccaccini Ipsita Roy 《Polymer International》2016,65(6):661-674
Bioactive glass is considered an ideal material for haemostasis as it releases Ca2+ ions upon hydration, which is required to support thrombosis. In this study the effects of the presence of nanoscaled bioactive glass (n‐BG) in poly(3‐hydroxybutyrate) (P(3HB)) microsphere films on the structural properties, thermal properties and biocompatibility of the films were studied. The n‐BG with a high surface area was also tested for its in vitro haemostatic efficacy and was found to be able to successfully reduce clot detection time. In an effort to study the effect of the roughness induced by the formation of hydroxyapatite on cellular functions such as cell adhesion, cell mobility and cell differentiation, the composite films were immersed in simulated body fluid for periods of 1, 3 and 7 days. From scanning electron microscopy images, the surface of the P(3HB)/n‐BG composite microsphere films appeared fairly uniform and smooth on day 1; however on day 3 and day 7 a rough and uneven surface was observed. The presence of hydroxyapatite on the composite microsphere films on day 3 and day 7 influenced the surface roughness of the films. However, when the P(3HB)/n‐BG composite microsphere films with enhanced surface roughness were tested for biocompatibility, reduced amounts of protein adsorption and cell adhesion were observed. This study thus revealed that there is an optimal surface roughness for the P(3HB) microsphere films for increased cell adhesion, beyond which it could be deleterious for cell adhesion and differentiation. © 2016 Society of Chemical Industry 相似文献
119.
Claire S. Whyte Akriti Rastogi Ellis Ferguson Michela Donnarumma Nicola J. Mutch 《International journal of molecular sciences》2022,23(6)
Loss of fibrinogen is a feature of trauma-induced coagulopathy (TIC), and restoring this clotting factor is protective against hemorrhages. We compared the efficacy of cryoprecipitate, and of the fibrinogen concentrates RiaSTAP® and FibCLOT® in restoring the clot integrity in models of TIC. Cryoprecipitate and FibCLOT® produced clots with higher maximal absorbance and enhanced resistance to lysis relative to RiaSTAP®. The fibrin structure of clots, comprising cryoprecipitate and FibCLOT®, mirrored those of normal plasma, whereas those with RiaSTAP® showed stunted fibers and reduced porosity. The hemodilution of whole blood reduced the maximum clot firmness (MCF) as assessed by thromboelastography. MCF could be restored with the inclusion of 1 mg/mL of fibrinogen, but only FibCLOT® was effective at stabilizing against lysis. The overall clot strength, measured using the Quantra® hemostasis analyzer, was restored with both fibrinogen concentrates but not cryoprecipitate. α2antiplasmin and plasminogen activator inhibitor-1 (PAI-1) were constituents of cryoprecipitate but were negligible in RiaSTAP® and FibCLOT®. Interestingly, cryoprecipitate and FibCLOT® contained significantly higher factor XIII (FXIII) levels, approximately three-fold higher than RiaSTAP®. Our data show that 1 mg/mL fibrinogen, a clinically achievable concentration, can restore adequate clot integrity. However, FibCLOT®, which contained more FXIII, was superior in normalizing the clot structure and in stabilizing hemodiluted clots against mechanical and fibrinolytic degradation. 相似文献
120.
Alessandra Bosutti Barbara Dapas Gabriele Grassi Rossana Bussani Fabrizio Zanconati Fabiola Giudici Cristina Bottin Nicola Pavan Carlo Trombetta Bruna Scaggiante 《International journal of molecular sciences》2022,23(8)
Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; p = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer. 相似文献