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41.
A Elbehti-Green HC Au JT Mascarello D Ream-Robinson IE Scheffler 《Canadian Metallurgical Quarterly》1998,213(1-2):133-140
The neurological manifestations of multiple sclerosis (MS) have been considered to result from demyelination of axons with relative preservation of axonal integrity. This concept has been challenged recently by a landmark pathological study, published in the New England Journal of Medicine, which has demonstrated that axonal degeneration is also present. The authors of the study hypothesized that axonal degeneration is the pathological correlate of the irreversible neurological impairment in this disease. However, this hypothesis cannot be reconciled with the clinical results obtained with transcranial applications of AC pulsed electromagnetic fields (EMFs) of picotesla flux density which have shown rapid and sustained improvement of symptoms including normalization of evoked potential responses in patients with chronic progressive or secondary progressive MS without demyelinated areas first undergoing remyelination or transected axons undergoing regeneration. Biochemical studies have shown that MS patients are serotonergically depleted with the extent of cerebral depletion correlating with the degree of motor disability and a chronic progressive course. It is believed that progressive serotonergic neuronal atrophy with synaptic inactivation, not axonal degeneration, are the hallmarks of the disease and that administration of AC pulsed magnetic fields improves symptoms of MS partly through reactivation of serotonergic neurons and amplification of synaptic serotonergic transmission. 相似文献
42.
Amphotericin B (AmB) is the most widely used polyene antibiotic to treat systemic fungal infections which affect an increasing number of immunocompromised patients. It is generally thought that AmB forms pores within the fungi membranes by interacting with ergosterol, the main sterol of fungi. However, it also interacts with the cholesterol contained in mammalian cells, hence its toxicity. In order to have a better understanding of the interactions prevailing between AmB and sterols, differential scanning calorimetry was used to study various mixtures incorporating from 6.5 to 25 mol% of AmB in pure dipalmitoylphosphatidylcholine (DPPC) vesicles and in ergosterol- or cholesterol-containing DPPC vesicles. The sterol concentration was kept constant at 12.5 mol% with respect to the phospholipid. Our results show that three phases co-exist when AmB is dispersed in the pure phospholipid. One corresponds to the phospholipid phase alone. The two others are characterised by a broad transition at temperatures higher than the main transition temperature of the pure phospholipid, corresponding to the drug in interaction with the aliphatic chains of the lipid. The fact that the transition temperatures of these additional components are higher than that of the pure phospholipid suggests that AmB interacts strongly with the aliphatic chains of the lipid, consistent with the idea prevailing in the literature that AmB by itself may form pores in a lipid matrix. When AmB interacts with cholesterol-containing bilayers the thermograms also present three components. Upon increasing the concentration of AmB, though, an important broadening of these components is observed which is explained in terms of destabilisation of the organisation of the aliphatic chains. The situation is strikingly different if ergosterol is present in the lipid matrix. The thermograms remain unmodified as the concentration of AmB is increased and a broad transition, now involving only two components when the thermograms are decomposed, is observed. An analysis of the results shows that various interacting units, e.g. AmB+DPPC and (AmB+ergosterol)+DPPC, are present within the membrane. These units involve the phospholipid and hence contribute to its structurisation. The important differences between the thermograms obtained with the ergosterol- as compared to the cholesterol-containing bilayers, in spite of the structural similarity of these two sterols, provides strong evidence for the selectivity of interaction of AmB with ergosterol as compared to cholesterol. It is thus clear that the action of AmB on cholesterol- as compared to ergosterol-containing membranes results from different mechanisms. Finally, UV-visible spectra of AmB in pure as well as sterol-containing DPPC vesicles show the presence of absorption bands that give support to the interpretation derived from the calorimetric data. 相似文献
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ML Nochomovitz AF Dimarco JT Mortimer NS Cherniack 《Canadian Metallurgical Quarterly》1983,127(3):325-329
We studied in 10 supine anesthetized dogs diaphragm contraction produced by electrical activation with intramuscular electrodes surgically implanted in the ventral surface of the diaphragm and compared this with activation of the ipsilateral phrenic nerve (C5, 6, and 7) before it entered the thorax. Repetitive 40-Hz pulse trains with supramaximal current stimulus were used after hyperventilation of the animals to apnea. A single intramuscular electrode within 1 to 2 cm of the site of phrenic nerve entry into the diaphragm produced a mean transdiaphragmatic pressure of 12.0 cm H2O +/- 0.97 SE and mean tidal volume of 0.27 L +/- 0.04 SE. Mean values observed with phrenic nerve stimulation were not statistically different, and both electrode systems produced equivalent outward abdominal motion and upper rib cage paradox, as monitored by inductive plethysmography. There was no difference in gas exchange during stimulation with a single hemidiaphragm electrode and mechanical ventilation compared at the same tidal volume and respiratory rate. Blockade of neuromuscular transmission with curare eliminated intramuscular and phrenic nerve stimulation proportionately, suggesting that activation of the diaphragm is dependent in both cases on the phrenic nerve. This technique does not entail manipulation of the phrenic nerve and may have clinical application as an alternative technique for diaphragm pacing. 相似文献
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JM Koelman HJ Noteborn de Goey LP BJ Verhaar JT Walraven 《Canadian Metallurgical Quarterly》1985,32(11):7195-7198
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