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71.
M Dong XQ Ding DI Pinon EM Hadac RP Oda JP Landers LJ Miller 《Canadian Metallurgical Quarterly》1999,274(8):4778-4785
The molecular basis of ligand binding to receptors provides important insights for drug development. Here, we explore domains of the cholecystokinin (CCK) receptor that are critical for ligand binding, using a novel series of fluorescent photolabile probes, receptor proteolysis, and rapid high resolution separation of peptide fragments by capillary electrophoresis. Each probe incorporated the same fluorophore and a photolabile p-benzoylphenylalanine at the amino terminus of the pharmacophoric domain (residue 24 of CCK-33) of CCK analogues representing full agonist, partial agonist, and antagonist of this receptor. Each was used to label the CCK receptor expressed on Chinese hamster ovary-CCKR cells, with the labeled domain then released by cyanogen bromide cleavage. Capillary electrophoresis with laser-induced fluorescence detection achieved an on-capillary mass sensitivity of 1.6 attomoles (10(-18) mol), with an excellent signal-to-noise ratio. Each of the biologically divergent, but structurally similar probes saturably and specifically labeled the same receptor domain, consistent with conservation of "docking" determinants. This had an apparent mass of 2.9 kDa, most consistent with the first extracellular loop domain. An additional probe having its site of covalent attachment in a different region of the probe (residue 29 of CCK-33) labeled a distinct receptor fragment with differential migration on capillary electrophoresis (third extracellular loop). Identification of the specific receptor residue(s) covalently linked to the amino-terminal probes must await further fragmentation and sequence analysis. 相似文献
72.
VL Cressman EM Hicks WK Funkhouser DC Backlund BH Koller 《Canadian Metallurgical Quarterly》1998,19(6):853-866
In the cystic fibrosis (CF) patient, lung function decreases throughout life as a result of continuous cycles of infection, particularly with Pseudomonas aeruginosa and Staphylococcus aureus. The mechanism underlying the pathophysiology of the disease in humans has not been established. However, it has been suggested that abnormal, tenacious mucus, resulting perhaps from improper hydration from loss of Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) protein, impairs clearance of bacteria from the CF airway and provides an environment favorable to bacterial growth. If this hypothesis is correct, it could explain the absence of respiratory disease in CFTR-deficient mice, since mice have only a single submucosal gland and display few goblet cells in their lower airways, even when exposed to bacteria. To test this hypothesis further, we induced allergic airway disease in CFTR-deficient mice. We found that induction of allergic airway disease in mice, unlike bacterial infection, results in an inflammatory response characterized by goblet cell hyperplasia, increased mucin gene expression, and increased production of mucus. However, we also found that disease progression and resolution is identical in Cftr-/- mice and control animals. Furthermore, we show that the presence of mucus in the Cftr-/- airway does not lead to chronic airway disease, even upon direct inoculation with S. aureus and P. aeruginosa. Therefore, factors in addition to the absence of high levels of mucus secretion protect the mouse from the airway disease seen in human CF patients. 相似文献
73.
Refusal to eat by the elderly, and subsequent malnutrition, occurs in both institutional and community settings. Causes include physiologic changes associated with aging, mental disorders such as dementia and depression, and medical, social, and environmental factors. Treatment approaches call for management of these causes while considering the roles that medicine, ethics, and culture play in the process. 相似文献
74.
EM Burtsev LA Zhdanova TV Riabchikova EV Batanova NB Fokina GN Gromtseva 《Canadian Metallurgical Quarterly》1998,98(9):9-11
90 infants with intrauterine growth retardation (IGR) and 100 normal infants (control group) were followed up from 5 days till 3 years of life. In IGR infants there was a more frequent combination of several neurologic syndromes, an early manifestation of motor disorders (from the very moment of birth), a delay of neuro-psychic development (during the first year of life), a tendency to development of moderate hydrocephalus by the age of 6 months. Autonomic-visceral disorders in them were mostly characterized by the symptoms of abaissement, but not of irritation. 相似文献
75.
A Martin M State K Koenig R Schultz EM Dykens SB Cassidy JF Leckman 《Canadian Metallurgical Quarterly》1998,155(9):1265-1273
76.
EM Manno DR Gress LH Schwamm MN Diringer CS Ogilvy 《Canadian Metallurgical Quarterly》1998,29(2):422-428
BACKGROUND AND PURPOSE: Transcranial doppler ultrasound (TCD) is used after subarachnoid hemorrhage to detect cerebral vasospasm and is often treated with induced hypertension. Cerebral autoregulation, however, may be disturbed in this population, raising the possibility that TCD velocities may be elevated by induced hypertension. To study this possibility, we performed continuous TCD monitoring of the middle cerebral artery during the induction and withdrawal of induced hypertension in patients after subarachnoid hemorrhage. METHODS: Twenty-eight patients were studied during the induction and withdrawal of hypertension using primarily phenylephrine. Continuous monitoring was performed on the middle cerebral artery with the highest flow velocity. Treatment was based on rising TCD velocities or clinical evidence for cerebral vasospasm. Mean arterial pressure and mean TCD velocities were recorded every minute. A change of > 15% from starting TCD values was considered significant. Cerebral autoregulation was calculated as a percentage of intact autoregulation. Patients were subsequently divided into groups of disturbed and intact autoregulation. RESULTS: In 10 of 19 patients (53%), TCD velocities changed by > 15% and paralleled changes in mean arterial pressure. This directly altered the TCD interpretation of the grade of vasospasm in 7 of 19 patients (36%). Three additional patients had smaller absolute changes in TCD velocities. No clinical difference could be identified between patients with disturbed and intact autoregulation. CONCLUSIONS: In patients with disturbed autoregulation after subarachnoid hemorrhage, induced hypertension can alter cerebral blood flow velocities. The level of autoregulation needs to be considered when interpreting TCD velocities in patients after subarachnoid hemorrhage. 相似文献
77.
EA Hassink AT Brugman-Boezeman LM Robbroeckx PN Rieu EM van Kuyk PM Wels C Festen 《Canadian Metallurgical Quarterly》1998,13(5-6):377-383
Parents play a crucial role in the life of a child suffering from an anorectal malformation (ARM), since their guidance contributes to the degree to which the child learns to cope with his or her disability. We investigated whether they experience stress in parenting such a child and also attempted to identify somatic or behavioral characteristics in the child that influence the stress of parenting. The parents of 109 children (69 males, 40 females; median age 5.9 years, range 1-18 years) with an ARM (58 low, 10 intermediate, 41 high) were studied. The Nijmegen Questionnaire on Child-rearing Situations (NQCS) was used to investigate the existing parenting situation. Behavioral characteristics of the children were studied by means of the Child Behaviour Checklist (CBCL) and the Teacher Report Form (TRF). In a semi-structured interview, we investigated how parents experienced the implications of the disability in everyday life with their child. Our study showed that as far as the perception of parenting stress is concerned, parents of children with an ARM do not differ from those with healthy primary-school children. Within the group of parents with ARM-afflicted children, the parents of older, incontinent children experienced relatively more stress, especially when the child concerned was male. With regard to the children's behavior, the parents and teachers under investigation did not report a higher than normal incidence of deviant behavior. However, when individual parents observed difficult behavior in their child, they found it harder to deal with than the incontinence for feces. Regarding the implications of the disorder for their everyday lives, parents were concerned and indicated a need for specific counselling. We conclude that having a child with a somatic affliction, in this case an ARM, does not automatically imply that the parents experience child-rearing problems. However, certain groups of parents are more at risk, i.e., parents with older, incontinent sons and parents with children exhibiting behavioral problems. In addition, our study shows that parents do have difficulties in coping with the implications of the disorder and express a need for support. We feel that patient care can be improved if aid is tailored to these specific problems. 相似文献
78.
Serum amyloid P component (SAP) is a glycoprotein in human plasma. We previously showed that SAP is specifically localized in human atherosclerotic lesions, suggesting that SAP may play a role in atherogenesis. In this study, the interactions between human SAP and high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were investigated by using a solid phase plate assay. Biotinylated SAP bound to immobilized HDL and VLDL in a calcium-dependent, saturable manner. The SAP-HDL and SAP-VLDL bindings reached saturation at 4 nM and 16 nM of SAP, respectively. The bindings were inhibited by native SAP in a dose-dependent manner. No binding between SAP and LDL was found in the presence of calcium or EDTA, which indicates the specificity of SAP-lipoproteins interactions. These results suggest that the function of SAP is related to its capability to interact with lipoproteins and this may have important implications in atherosclerosis and in amyloidosis. 相似文献
79.
80.