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BACKGROUND: We conducted a population-based case-control study to describe the relationship between occupational exposure to estrogenic chemicals and the occurrence of breast cancer in Cape Cod, Massachusetts. METHODS: Incident cases of breast cancer (n = 261) diagnosed from 1983 through 1986 and controls (n = 753) were interviewed to gather information on breast cancer risk factors and all full-time jobs held since age 18. Blinded exposure assessments were employed using the data from the NIOSH National Occupational Exposure Survey, chemical production and usage information, and the expert judgement of a certified industrial hygienist. RESULTS: Overall, 29.5% of cases and 32.5% of controls had probable occupational exposure to one or more xenoestrogens. Probable exposure to nonylphenol (21.5% of cases, 21.4% of controls), butyl benzyl phthalate (10.0% of cases, 13.2% of controls), BHA (7.3% of cases, 9.6% of controls), bisphenol A (9.6% of cases, 11.6% of controls), and 4-tert-butylphenol (2.7% of cases and 5.3% of controls) were relatively commons, while probable exposure to the other xenestrogens was rare. Only PCBs and 4-octylphenol were associated with moderate increase in the odds of breast cancer (PCBs: 5 exposed cases and 6 exposed controls, adjust odds ratio: 3.2, 95% CI = 0.8-12.2, and 4-octylphenol: 6 exposed cases and 5 exposed controls, adjusted odds ratio: 2.9, 95% CI = 10.8).  相似文献   
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Bronchocentric granulomatosis (BCG) is a rare chronic granulomatous lung disease that leads to destruction of the airway walls. It has been observed in association with various conditions, but never, so far, been reported to involve the central nervous system. We report a case of histologically confirmed pulmonary bronchocentric granulomatosis temporally associated with a partial central diabetes insipidus (CDI). Although the pathological basis of the posterior pituitary gland involvement was not ascertained, the temporal association of bronchocentric granulomatosis and central diabetes insipidus, as well as the fact that corticosteroid treatment provided stable remission of both conditions after a 10 month follow-up, strongly suggest that central diabetes insipidus was aetiologically related to bronchocentric granulomatosis in this patient.  相似文献   
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This article focuses on the experiences and role of a tutor while conducting a problem based learning (PBL) exercise to facilitate the learning of biochemistry and molecular biology. A case presentation of sickle cell anemia was used to frame a module. The objective of this experimental exercise was to assess the suitability and effectiveness of problem based learning in the first year of undergraduate medical course and to practice self-assessment by tutors in this new role of a facilitator of learning through small group discussion. A tutor during such a learning session encouraged the students to apply their reasoning to analyze the problem and to develop self-directed learning skills in acquiring the knowledge appropriate to their perceived needs to work on a problem. The tutors ensured that they apply this knowledge in their work with other similar problems that they would encounter later in life.  相似文献   
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OBJECTIVE: To investigate the regulation of expression of the angiogenic cytokine vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA), in order to determine whether new blood vessel formation could be a potential therapeutic target in RA. METHODS: Dissociated RA synovial membrane cells were cultured in the presence of cytokine inhibitors, or under hypoxic conditions. Serum VEGF levels were serially measured in RA patients enrolled in clinical trials of anti-tumor necrosis factor alpha (anti-TNFalpha) monoclonal antibody treatment. RESULTS: Combined neutralization of TNFalpha and interleukin-1 (IL-1) in RA synovial membrane cultures reduced VEGF release by 45% (P < 0.05 versus control), although blockade of either TNFalpha or IL-1 activities alone resulted in only small inhibitory effects. In addition, release of VEGF from RA synovial membrane cells was selectively up-regulated by hypoxia. Serum VEGF levels were significantly elevated in RA patients relative to control subjects, and correlated with disease activity. Treatment of RA patients with anti-TNFalpha significantly decreased serum VEGF, and this effect was enhanced by cotreatment with methotrexate. CONCLUSION: Inhibition of TNFalpha and IL-1 activity in vivo could reduce the drive to new blood vessel formation, and hence pannus mass, adding to other therapeutic effects of anti-TNFalpha therapy in RA.  相似文献   
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OBJECTIVE: To determine whether a Pasteurella haemolytica A1 mutant that is unable to produce membrane lipoproteins has reduced susceptibility to complement-mediated killing, and to characterize the mutant strain. SAMPLE POPULATION: 12 sera from cattle resistant to P haemolytica challenge exposure after vaccination with P haemolytica or its antigens, or after natural exposure. PROCEDURES: Complement-mediated killing assays were performed, using wild-type and mutant strains and, as antibody source, various immune sera from cattle that were resistant to P haemolytica challenge exposure. Antibody response to whole-cell antigens produced by mutant and wild-type strains, production of outer membrane proteins and iron-regulated outer membrane proteins by the 2 strains, and growth of the 2 strains in various media were analyzed. RESULTS: Compared with wild-type P haemolytica, the lipoprotein mutant strain had increased susceptibility to bovine complement-mediated killing. Aside from the lipoproteins that are not produced by the mutant, immunoblot analysis did not reveal differences between immunoreactive antigens that are produced by the 2 strains. Some iron-regulated, outer membrane proteins, which usually are only produced by P haemolytica under iron-deficient conditions, were produced constitutively by the mutant. The mutant grew to a lower final cell density and at a lower rate under conditions likely to reflect those encountered in vivo. CONCLUSIONS: Lack of 3 membrane lipoproteins resulted in enhanced susceptibility to bovine complement-mediated killing. Site-specific mutagenesis of genes encoding P haemolytica membrane lipoproteins alters production of iron-regulated outer membrane proteins by P haemolytica. Growth characteristics of the mutant suggested that it may have reduced capacity for survival in vivo.  相似文献   
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Dosing regimen is an important determinant of both drug cost and patient compliance. This retrospective analysis evaluated dosing regimens and drug acquisition costs for 101 patients identified from medical records in a large metropolitan hospital as having hypertension and/or benign prostatic hyperplasia and receiving alpha-blocker therapy with either doxazosin or terazosin. Although once-daily administration is generally recommended for both drugs, 25 (38%) of 66 patients receiving terazosin were treated twice daily compared with 6 (17%) of 35 patients treated twice daily with doxazosin. This difference was statistically significant. The average (mean +/- SD) daily treatment cost per patient for all individuals receiving terazosin during the period of the record review was $1.68 +/- 0.60. For patients treated with doxazosin, the average was $0.96 +/- 0.65-a highly statistically significant result. If all 66 patients receiving terazosin had been converted to doxazosin at the beginning of the study, annual savings would have been $17,345.00. These results demonstrate the importance of reviewing actual dosing regimens. The fact that doxazosin could be administered to a significantly higher percentage of patients once daily rather than twice daily substantially decreased its cost relative to terazosin. A once-daily treatment regimen may also enhance patient compliance, thereby improving the chances of therapeutic success.  相似文献   
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