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991.
Thijs W. de Vos Dian Winkelhorst Hans J. Baelde Kyra L. Dijkstra Rianne D. M. van Bergen Lotte E. van der Meeren Peter G. J. Nikkels Leendert Porcelijn C. Ellen van der Schoot Gestur Vidarsson Michael Eikmans Rick Kapur Carin van der Keur Leendert A. Trouw Dick Oepkes Enrico Lopriore Marie-Louise P. van der Hoorn Manon Bos Masja de Haas 《International journal of molecular sciences》2021,22(13)
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth. 相似文献
992.
Rocío Mato-Basalo Miriam Morente-Lpez Onno J Arntz Fons A. J. van de Loo Juan Fafin-Labora María C. Arufe 《International journal of molecular sciences》2021,22(7)
Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature. 相似文献
993.
Luiza Ghila Thomas Aga Legy Andreas Frslev Mathisen Shadab Abadpour Joao A. Paulo Hanne Scholz Helge Rder Simona Chera 《International journal of molecular sciences》2021,22(7)
The past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease progression. Extracellular glucose is known to influence cell identity by impacting the redox balance. Here, we use global proteomics and pathway analysis to map the response of differentiating human pancreatic progenitors to chronically increased in vitro glucose levels. We show that exogenous high glucose levels impact different protein subsets in a concentration-dependent manner. In contrast, regardless of concentration, glucose elicits an antipodal effect on the proteome landscape, inducing both beneficial and detrimental changes in regard to achieving the desired islet cell fingerprint. Furthermore, we identified that only a subgroup of these effects and pathways are regulated by changes in redox balance. Our study highlights a complex effect of exogenous glucose on differentiating pancreas progenitors characterized by a distinct proteome signature. 相似文献
994.
Roua Hassoun Heidi Budde Hans Georg Mannherz Mria Ldi Setsuko Fujita-Becker Kai Thorsten Laser Anna Grtner Karin Klingel Desire Mhner Robert Stehle Innas Sultana Thomas Schaaf Mario Majchrzak Verena Krause Christian Herrmann Marc M. Nowaczyk Andreas Mügge Gabriele Pfitzer Rasmus R. Schrder Nazha Hamdani Hendrik Milting Kornelia Jaquet Diana Cimiotti 《International journal of molecular sciences》2021,22(17)
Rare pediatric non-compaction and restrictive cardiomyopathy are usually associated with a rapid and severe disease progression. While the non-compaction phenotype is characterized by structural defects and is correlated with systolic dysfunction, the restrictive phenotype exhibits diastolic dysfunction. The molecular mechanisms are poorly understood. Target genes encode among others, the cardiac troponin subunits forming the main regulatory protein complex of the thin filament for muscle contraction. Here, we compare the molecular effects of two infantile de novo point mutations in TNNC1 (p.cTnC-G34S) and TNNI3 (p.cTnI-D127Y) leading to severe non-compaction and restrictive phenotypes, respectively. We used skinned cardiomyocytes, skinned fibers, and reconstituted thin filaments to measure the impact of the mutations on contractile function. We investigated the interaction of these troponin variants with actin and their inter-subunit interactions, as well as the structural integrity of reconstituted thin filaments. Both mutations exhibited similar functional and structural impairments, though the patients developed different phenotypes. Furthermore, the protein quality control system was affected, as shown for TnC-G34S using patient’s myocardial tissue samples. The two troponin targeting agents levosimendan and green tea extract (-)-epigallocatechin-3-gallate (EGCg) stabilized the structural integrity of reconstituted thin filaments and ameliorated contractile function in vitro in some, but not all, aspects to a similar degree for both mutations. 相似文献
995.
The corrosion behaviour of laser surface cladding made from 304L stainless steel alloyed with varying concentrations of ruthenium in 1M HCl at 25°C was evaluated, fresh and after 12 hours, by electrochemical tests including open circuit potential and potentiodynamic polarisation scans. The ruthenium concentration in the 800?µm cladded layer varied from 0.82?wt-% to 4.67?wt-% ruthenium. The ruthenium doped samples were compared against a 304L stainless steel laser surface cladding with no ruthenium, 304L stainless steel samples with no laser cladding, 316L stainless steel, SAF2205 duplex stainless steel and Hastelloy C276®. Initial passivation was not observed in the 1M HCl but after 12 hours the addition of ruthenium led to reduced corrosion rates and improved passivation characteristics compared to the surface cladding without ruthenium. An optimum ruthenium range was observed between 3?wt-% and 5?wt-%. It was shown that at this optimum concentration, the ruthenium containing stainless steel clad on 304L stainless steel can compete commercially with the SAF2205 and Hastelloy C276® as long as the clad is 200?µm or less. 相似文献
996.
Jacco van de Streek Paul Verwer René de Gelder Frank Hollander 《Journal of the American Oil Chemists' Society》1999,76(11):1333-1341
The structural elements of the β′-2 polymorph of 1,3-dilauroyl-2-myristoylglycerol as found by Birker et al. (J. Am. Oil Chem. Soc. 68:895–906, 1991) were also observed in the crystal structures of other long-chain compounds. This analogy led to the assembly
of a β′-2 structure at the atomic level from known crystallographic data. The structure was optimized by molecular mechanics
and was consistent with experimental data, including satisfactory reproduction of the X-ray powder pattern. To the best of
our knowledge, this is the first β′ structure with a 1,2 configuration and an intramolecular orthorhombic subcell which is
fully optimized by molecular mechanics to date. It shows all structural elements found earlier by Birker et al. 相似文献
997.
Kees van Malssen Arjen van Langevelde René Peschar Henk Schenk 《Journal of the American Oil Chemists' Society》1999,76(6):669-676
A complete isothermal phase-transition scheme of cocoa butter under static conditions is presented, based on time-resolved
X-ray powder diffraction experiments. In contrast to what is known from literature, not only β V, but also β VI can be obtained
directly through transformation from β′. Another remarkable result is that β′ exists as a phase range rather than as two separate
phases. Within this β′ phase range no isothermal phase transitions have been observed. More detailed information concerning
the observed cocoa butter polymorphs was obtained by determination of melting ranges, using time-resolved X-ray powder diffraction.
Also standard X-ray powder diffraction patterns of the γ, the α, and the two β phases and parts of the β′ phase range have
been recorded. The observed phase behavior of cocoa butter has been explained based on the concept of individual crystallite
phase behavior of cocoa butter 相似文献
998.
Electrodeposition of PbO2 and Bi–PbO2 on Ebonex was carried out under various conditions, and the surfaces and coating/substrate interfaces examined by SEM, XPS and SIMS. Excellent adhesion to Ebonex was obtained with both crystalline and amorphous surfaces. Low plating temperatures resulted in dark grey, bright PbO2 and black, mirror-like Bi–PbO2 surfaces. Extrapolation of electrode lifetime test data indicated corrosion rates of 716 m yr–1 for PbO2 and 158 m yr–1 for Bi–PbO2. 相似文献
999.
Polymorphism of milk fat studied by differential scanning calorimetry and real-time X-ray powder diffraction 总被引:2,自引:7,他引:2
E. ten Grotenhuis G. A. van Aken K. F. van Malssen H. Schenk 《Journal of the American Oil Chemists' Society》1999,76(9):1031-1039
The crystallization behavior of milk fat was investigated by varying the cooling rate and by isothermal solidification at
various temperatures while monitoring the formation of crystals by differential scanning calorimetry (DSC) and X-ray powder
diffraction (XRD). Three different polymorphic crystal forms were observed in milk fat: γ, α, and β′. The β-form, occasionally
observed in previous studies, was not found. The kind of polymorph formed during crystallization of milk fat from its melted
state was dependent on the cooling rate and the final temperature. Moreover, transitions between the different polymorphic
forms were shown to occur upon storing or heating the milk fat. The characteristic DSC heating curve of milk fat is interpreted
on the basis of the XRD measurements, and appears to be a combined effect of selective crystallization of triglycerides and
polymorphism. 相似文献
1000.
Janssen Marcel J.W.; van de Wiel Wendy A.E.C.; Beiboer Sigrid H.W.; van Kampen Muriel D.; Verheij Hubertus M.; Slotboom Arend J.; Egmond Maarten R. 《Protein engineering, design & selection : PEDS》1999,12(6):497-503
The catalytic contribution of His48 in the active site of porcinepancreatic phospholipase A2 was examined using site-directedmutagenesis. Replacement of His48 by lysine (H48K) gives riseto a protein having a distorted lipid binding pocket. Activityof this variant drops below the detection limit which is 107-foldlower than that of the wild-type enzyme. On the other hand,the presence of glutamine (H48Q) or asparagine (H48N) at thisposition does not affect the structural integrity of the enzymeas can be derived from the preserved lipid binding propertiesof these variants. However, the substitutions H48Q and H48Nstrongly reduce the turnover number, i.e. by a factor of 105.Residual activity is totally lost after addition of a competitiveinhibitor. We conclude that proper lipid binding on its ownaccelerates ester bond hydrolysis by a factor of 102. With theselected variants, we were also able to dissect the contributionof the hydrogen bond between Asp99 and His48 on conformationalstability, being 5.2 kJ/mol. Another hydrogen bond with His48is formed when the competitive inhibitor (R)-2-dodecanoylamino-hexanol-1-phosphoglycolinteracts with the enzyme. Its contribution to binding of theinhibitor in the presence of an interface was found to be 5.7kJ/mol. 相似文献