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81.
Synthesis and Biological Evaluation of Benzo[b]furans as Inhibitors of Tubulin Polymerization and Inducers of Apoptosis
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Dr. Ahmed Kamal N. V. Subba Reddy V. Lakshma Nayak V. Saidi Reddy B. Prasad Vijaykumar D. Nimbarte Vunnam Srinivasulu M. V. P. S. Vishnuvardhan Prof. C. Suresh Reddy 《ChemMedChem》2014,9(1):117-128
A series of benzo[b]furans was synthesized with modification at the 5‐position of the benzene ring by introducing C‐linked substituents (aryl, alkenyl, alkynyl, etc.). These compounds were evaluated for their antiproliferative activities, inhibition of tubulin polymerization, and cell‐cycle effects. Some compounds in this series displayed excellent activity in the nanomolar range against lung cancer (A549) and renal cell carcinoma (ACHN) cancer cell lines. (6‐Methoxy‐5‐((4‐methoxyphenyl)ethynyl)‐3‐methylbenzofuran‐2‐yl)(3,4,5‐trimethoxyphenyl)methanone ( 26 ) and (E)‐3‐(6‐methoxy‐3‐methyl‐2‐(1‐(3,4,5‐trimethoxyphenyl)vinyl)benzofuran‐5‐yl)prop‐2‐en‐1‐ol ( 36 ) showed significant activity in the A549 cell line, with IC50 values of 0.08 and 0.06 μM , respectively. G2/M cell‐cycle arrest and subsequent apoptosis was observed in the A549 cell line after treatment with these compounds. The most active compound in this series, 36 , also inhibited tubulin polymerization with a value similar to that of combretastatin A‐4 (1.95 and 1.86 μM , respectively). Furthermore, detailed biological studies such as Hoechst 33258 staining, DNA fragmentation and caspase‐3 assays, and western blot analyses with the pro‐apoptotic protein Bax and the anti‐apoptotic protein Bcl‐2 also suggested that these compounds induce cell death by apoptosis. Molecular docking studies indicated that compound 36 interacts and binds efficiently with the tubulin protein. 相似文献
82.
Recent changes in the construction of building floors have included the use of light material composite systems and long span floor systems. Although these changes have many advantages, such floor systems can suffer from excessive vibration due to human activities. This problem is exacerbated in office buildings due to the reduction in inherent damping associated with modern fit outs. Excessive floor vibrations are often realised after the completion of construction or following structural modifications and normally arise due to inadequate knowledge of the damping values in the design process. Thus rectification measures are normally required to reduce floor accelerations. This paper proposes a new innovative passive viscoelastic damper to reduce floor vibrations. This damper can be easily tuned to the fundamental frequency of the floor and can be designed to achieve various damping values. The paper discusses the analytical development of the damper with experimental results presented on a prototype to demonstrate its effectiveness. 相似文献
83.
JS Bertino S Thoelen P VanDamme JP Bryan PR Becherer S Frey FG Hayden LC Marcus DM Parenti M Sperling IS Chan L Brown D Nalin 《Canadian Metallurgical Quarterly》1998,178(4):1181-1184
The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels. 相似文献
84.
GH Sture RE Halliwell KL Thoday AH van den Broek JI Henfrey DH Lloyd IS Mason E Ferguson 《Canadian Metallurgical Quarterly》1995,44(3-4):293-308
Results of intradermal skin test responses to the same panel of 53 allergens were compared in 118 dogs with atopic disease presented at two geographical centres, Edinburgh (87 cases) and London (31 cases). The allergens most commonly positive at both centres were human dander and Dermatophagoides farinae, but positive tests to all of the allergens used occurred in at least one case. The mean number of allergens to which positive tests resulted in atopic dogs was 5.126 (Edinburgh) and 5.129 (London). The majority of animals were sensitive to allergens from more than one group. A significantly higher number of positive reactors to house dust allergen was observed at London than at Edinburgh (P < 0.05), while a significantly higher number of positive reactions to grass pollens was detected at Edinburgh than in London (P < 0.05). Sensitivity to Dermatophagoides pteronyssinus, in the absence of sensitivity to D. farinae, was uncommon and therefore both of these mite allergens should be incorporated in intradermal skin testing panels in Great Britain. 相似文献
85.
GI Cubero JJ Reguero A Batalla E Simarro IS Posada S Braga JL Negrete 《Canadian Metallurgical Quarterly》1998,53(5):269-273
Therapeutic interventions in the skeletal system are an essential part of interventional radiology. Although in terms of figures these procedures are applied less frequently, they are very effective. Percutaneous transarterial embolization of a spinal tumor is well-established interventional treatment. It is primary treatment for preoperative devascularization, but also for palliation of pain and for reduction of tumor volume. As an alternative access for embolization, direct percutaneous puncture of a vertebra is used. A new and promising technique is vertebroplasty, the percutaneous injection of acrylic surgical cement in destroyed vertebrae. The present paper discusses indications, technique, results and complications of these interventional therapeutic modalities in the treatment of primary and secondary spinal tumors. 相似文献
86.
This paper aims to explore the influence of the immune system on the pathobiochemistry of movement disorders (Tourette syndrome, obsessive compulsive disorders and attention-deficit disorder, with and without hyperactivity) and schizophrenia. In children, a temporal relationship has been observed between contraction of a group A beta-hemolytic streptococcal infection and subsequent presentation with one of the movement disorders. Pathology investigations reveal that elevated antineuronal antibodies are associated with movement disorders. Similarly, elevations in interleukin-1 beta and interleukin-6 have been reported in schizophrenia. It is now known that the immune system can be activated by conditions other than a viral or bacterial infection, such as: neurological insult, neurotoxicity--endogenous and environmental, neurotransmitter and cholesterol dysregulation. These latter avenues of immune system activation will be explored with respect to schizophrenia. 相似文献
87.
The whole-cell patch-clamp technique was used to voltage clamp acutely isolated myocytes at -60 mV and study effects of ionic environment on Na/K pump activity. In quiescent guinea pig myocytes, normal intracellular Na+ is approximately 6 mM, which gives a total pump current of 0.25 +/- 0.09 pA/pF, and an inward background sodium current of 0.75 +/- 0.26 pA/pF. The average capacitance of a cell is 189 +/- 61 pF. Our main conclusion is the total Na/K pump current comprises currents from two different types of pumps, whose functional responses to the extracellular environment are different. Pump current was reversibly blocked with two affinities by extracellular dihydro-ouabain (DHO). We determined dissociation constants of 72 microM for low affinity (type-1) pumps and 0.75 microM for high affinity (type-h) pumps. These dissociation constants did not detectably change with two intracellular Na+ concentrations, one saturating and one near half-saturating, and with two extracellular K+ concentrations of 4.6 and 1.0 mM. Ion effects on type-h pumps were therefore measured using 5 microM DHO and on total pump current using 1 mM DHO. Extracellular K+ half-maximally activated the type-h pumps at 0.4 mM and the type-1 at 3.7 mM. Extracellular H+ blocked the type-1 pumps with half-maximal blockade at a pH of 7.71 whereas the type-h pumps were insensitive to extracellular pH. Both types of pumps responded similarly to changes in intracellular-Na+, with 9.6 mM causing half-maximal activation. Neither changes in intracellular pH between 6.0 and 7.2, nor concentrations of intracellular K+ of 140 mM or below, had any effect on either type of pump. The lack of any effect of intracellular K+ suggests the dissociation constants are in the molar range so this step in the pump cycle is not rate limiting under normal physiological conditions. Changes in intracellular-Na+ did not affect the half-maximal activation by extracellular K+, and vice versa. We found DHO-blockade of Na/K pump current in canine ventricular myocytes also occurred with two affinities, which are very similar to those from guinea pig myocytes or rat ventricular myocytes. In contrast, isolated canine Purkinje myocytes have predominantly the type-h pumps, insofar as DHO-blockade and extracellular K+ activation are much closer to our type-h results than type-1. These observations suggest for mammalian ventricular myocytes: (a) the presence of two types of Na/K pumps may be a general property. (b) Normal physiological variations in extracellular pH and K+ are important determinants of Na/K pump current. (c) Normal physiological variations in the intracellular environment affect Na/K pump current primarily via the Na+ concentration. Lastly, Na/K pump current appears to be specifically tailored for a tissue by expression of a mix of functionally different types of pumps. 相似文献
88.
The role of intramuscular botulinum toxin A in the treatment of 26 children with cerebral palsy was evaluated. The indication for injection was the presence of a dynamic contracture of lower-limb muscles interfering with positioning or walking. Spastic target muscles were identified by clinical examination and, in ambulant children, by gait analysis. Between 50 and 320 units of botulinum toxin were injected into each muscle group to a total dose of 100 to 400 units per child. The effects of injection were monitored by repeated clinical examination and gait analysis. There were no clinically detectable systemic side-effects, and all but one patient had a reduction in tone, which occurred within three days and persisted for two to four months. There were significant improvements in ambulatory status and in sagittal-plane kinematics. In some cases these gains persisted after the tone-reducing effects of the toxin had worn off. 相似文献
89.
Systemic amyloidosis normally has a dismal prognosis. However, there are several case reports of protracted survival, usually as a response to measures designed to retard the further deposition of amyloid fibrils. In AA amyloid, most commonly associated with inflammatory rheumatological, bowel, and chest diseases, such interventions have had some success, but the dramatic response of complete resolution of nephrotic syndrome as a result of the regular institution of postural chest drainage and antibiotic therapy, in the clinical context of bronchiectasis, has been previously reported only once. In both of our cases, after protracted remission, such therapy was abandoned by the patients, leading both to recurrence of nephrotic syndrome and also eventually to end-stage renal failure requiring dialysis. 相似文献
90.
To gain more insight into decision making around the termination of resuscitation (CPR), we studied factors which influenced the time before discontinuing resuscitation, and the criteria on which those decisions were based. These criteria were compared with those of the European Resuscitation Council (ERC) and the American Heart Association (AHA). For this study, we reviewed the audiotapes of resuscitation attempts in a hospital. A total of 36 attempts were studied, involving 27 men and nine women, mean (S.D.) age 64 (18) years. A total of 19 patients received resuscitation on general wards, and 17 in the emergency room after an out-of-hospital circulatory arrest. The median interval time (range) from start to termination was 33 min (8-81 min). Results from multiple linear regression showed that a delay greater than 5 min in first advanced life support measures, drawing a sample for biochemical analysis, and the patient's response shown by return of spontaneous circulation were independently associated with the time of terminating resuscitation. The team used a number of criteria which can be found in the guidelines of the ERC and the AHA, but also used additional criteria. The ERC and the AHA criteria were not sufficient to cover all termination decisions. We conclude that the point in time to terminate resuscitation is not always rationally chosen. Updating of the current guidelines for terminating resuscitation and training resuscitation teams to use these guidelines is recommended. 相似文献