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排序方式: 共有282条查询结果,搜索用时 15 毫秒
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OBJECTIVE: With the development of growth hormone (GH) releasing agents and their use in human subjects, it is clear that these agents are not specific for GH release. More recent studies in humans have demonstrated acute increases in adrenocorticotrophic hormone (ACTH), cortisol and prolactin (PRL) after boluses of intravenous or subcutaneous GHRPs. The potential adverse effects of repeated episodes of transient hyperprolactinaemia and hypercortisolaemia during long-term therapy with growth hormone releasing peptides (GHRPs) and similar agents have raised concern. We have therefore assessed the impact of chronic hexarelin administration on the pituitary-adrenal axis and serum prolactin levels. DESIGN: Each subject received twice-daily subcutaneous hexarelin therapy (1.5 micrograms/kg body weight) for 16 weeks. The ACTH, cortisol and PRL responses to the morning subcutaneous injection of hexarelin were assessed. Hexarelin was administered at time 0 and blood samples were taken at -10, 0, 10, 20, 30, 40, 50, 60, 90, 120, 170 and 180 min. The ACTH and PRL responses were assessed at baseline and after 16 weeks of therapy. The cortisol response was assessed at baseline, 16 weeks and also 4 weeks after completion of hexarelin therapy. Basal levels of cortisol binding globulin (CBG), 24-h urinary free cortisol (UFC) estimations, thyroid stimulating hormone (TSH) and total thyroxine (TT4) were performed at baseline, weeks 16 and 20. RESULTS: The mean (+/- SEM) area under the cortisol curve (AUCCORT) at baseline, week 16 and week 20 were 1506 (+/- 77) nmol/l/h, 1222 (+/- 92) nmol/l/h and 1586 (+/- 58) nmol/l/h, respectively. There was a significant change in AUCCORT over the study period (P = 0.008). Compared with baseline, AUCCOPRT had decreased significantly (P < 0.05) after 16 weeks of hexarelin therapy. Four weeks after completion of hexarelin therapy, the AUCCORT increased significantly compared with AUCCORT at week 16 (P < 0.01) and was no longer significantly different from baseline values. There were no significant changes in UFC (P = 0.3), basal cortisol measurements (P = 0.19), area under the ACTH curve (AUCACTH) (P = 0.24) or CBG (P = 0.6) over the study period. The mean (+/- SEM) area under the PRL curve (AUCPRL) at the baseline and week 16 were 624 (+/- 82) mU/l/h and 641 (+/- 83) mU/l/h, respectively. There was no significant change in AUCPRL over the study period (P = 0.35). CONCLUSION: The present study demonstrates clearly that in this hexarelin dosage regimen, over-stimulation of the pituitary adrenal axis and prolactin secretion do not occur. In fact the impact of chronic hexarelin therapy on the pituitary-adrenal axis, i.e. decreased AUCCORT, contradict the findings reported after acute hexarelin administration and cannot be explained by changes in CBG. The lack of change in UFC, however, suggests that these changes are unlikely to be of clinical significance although the underlying mechanism requires further study. 相似文献
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CR Valeri G Ragno LE Pivacek R Srey JR Hess LE Lippert F Mettille R Fahie EM O''Neill IO Szymanski 《Transfusion》2002,42(12):1618-1618
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Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets 总被引:8,自引:0,他引:8
FC Chao ; BK Kim ; AM Houranieh ; FH Liang ; MW Konrad ; SN Swisher ; JL Tullis 《Transfusion》1996,36(6):536-542
BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia. 相似文献
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Theodore C. Bania MD MS Jason Chu MD Dallas Bailes MD Melanie O''Neill MD 《Academic emergency medicine》2004,11(4):335-338
Treatment of patients following an organophosphate (OP) exposure can deplete a hospital's entire supply of atropine. Given the possibility of multiple severe exposures after a terrorist attack using OP nerve agents, there exists a need for either greater atropine stores or the development of alternative antidotes. Jimson weed (Datura stramonium) contains atropine and other anticholinergic compounds and is common and readily available. It is used recreationally for its central anticholinergic effects and is made easily into an extract by boiling the crushed seeds. The extract has rapid onset of effects and may be useful for treatment of OP poisoning. OBJECTIVES: To determine whether pretreatment with an easily stored and prepared Datura seed extract (DSE) will increase survival following a severe OP poisoning. METHODS: Datura stramonium seeds were collected, crushed, and then heated in water to make a 2-mg/mL atropine solution (100 seeds contain approximately 6 mg of atropine or 0.007 mg/seed). Male rats were randomized to pretreatment with either saline (n = 10) or 7.5 mg/kg DSE (n = 10) given as a single intraperitoneal injection 5 minutes prior to a subcutaneous injection of 25 mg/kg of dichlorvos. The endpoint was time to death recorded by a blinded observer. RESULTS: The Kaplan-Meier estimates of the 24-hour survival rate was 90% (95% CI = 56% to 100%) for the DSE-pretreated group and 10% (95% CI = 0% to 45%) for the control group. The log-rank test revealed a statistically significant longer survival for the Datura-treated animals (p = 0.0002). Median survival time was 22 minutes 30 seconds for the control group and greater than 24 hours for the DSE-pretreated group. CONCLUSIONS: Pretreatment with DSE significantly increases survival following severe dichlorvos exposure. 相似文献
27.
Adenylate cyclase and guanylate cyclase activity in normal and leukemic human lymphocytes 总被引:1,自引:0,他引:1
Adenylate cyclase (AC) and guanylate cyclase (GC) activities were studied in normal B-enriched and T-enriched lymphocytes, in lymphocytes of children with acute lymphocytic leukemia (ALL), and in lymphocytes of adults with chronic lymphocytic leukemia (CLL). AC activity was greater in normal B than T lymphocytes (215 pmole/min/mg protein versus 80 pmole in the membrane-enriched fraction) and i both increased greatly after stimulation with isoproterenol and more so with prostaglandins E and F2 alpha. In leukemic lymphocytes, AC showed depressed activity (20 pmole in ALL cells and 55 pmole in CLL cells) and was less sensitive to hormonal stimulation: this loss of sensitivity occurred to a greater extent in ALL than in CLL lymphocytes. GC activity was greater in normal T than B cells (in membrane-enriched fraction: 10.2 pmole versus 5.3 pmole). It increased little with isoproterenol and prostaglandins stimulation, and much more with sodium azide and dehydroascorbic acid stimulation. GC activity was increased in both types of leukemic lymphocytes (23 pmole for ALL cells and 18 pmole for CLL cells) and was insensitive to stimulation. Possible derangement of cyclase and cyclic nucleotide regulation in leukemic cells is suggested. 相似文献
28.
Elastolytic activity of alveolar macrophages in chronic bronchitis: comparison of current and former smokers 总被引:1,自引:1,他引:1 下载免费PDF全文
We have compared the macrophage elastolytic activity of a group of current and former smokers with irreversible airflow obstruction. Elastolytic activity was determined in an initial bronchoalveolar lavage cell population and in alveolar macrophages cultured for three days, to investigate whether enhanced macrophage elastolytic activity alone is a determining factor in the susceptibility of some smokers to obstructive lung disease. Twenty current smokers and 12 former smokers who had abstained from smoking for at least three years were studied. All patients had spirometric evidence of irreversible air flow obstruction. Current smokers had a cell yield (mean +/- SD) of 138.7 +/- 36.4 X 10(6) cells (alveolar macrophages 94.2% +/- 2.1%) compared with 31.4 +/- 14.1 X 10(6) cells (macrophages 86.5% +/- 4.7%) in former smokers. Elastolytic activity in the initial lavage cell population from current and former smokers, measured with the synthetic elastase substrate succinyl-L-alanyl-L alanyl-L-alanine-p-nitroanilide, and expressed as the equivalent of 1 microgram of porcine pancreatic elastase, was respectively 0.113 +/- 0.003 and 0.096 +/- 0.004 microgram pancreatic elastase/mg cell protein. After three days in culture macrophage elastolytic activity in the current and former smokers' cells was respectively 0.107 +/- 0.006 and 0.011 +/- 0.001 microgram pancreatic elastase/mg cell protein (p less than 0.05). The elastase activity of the cultured alveolar macrophages from five current smokers had the inhibitor profile of a metalloproteinase. Our results indicate that enhanced macrophage elastolytic activity alone is not a determining factor in the susceptibility of some smokers to develop obstructive lung disease. 相似文献
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Infective conjunctivitis and corneal scarring in three brothers with sex linked hypogammaglobulinaemia (Bruton''s disease). 下载免费PDF全文
T T Hansel D P O''Neill M L Yee J M Gibson R A Thompson 《The British journal of ophthalmology》1990,74(2):118-120
The ocular findings in three brothers with Bruton's disease are reported. All three boys had purulent conjunctivitis, but the two older brothers also developed marked corneal scarring with visual impairment. Haemophilus influenzae was cultured from conjunctival swabs; it was resistant to neomycin but sensitive to chloramphenicol. Tear analysis showed that the three subjects had normal levels of lysozyme but no detectable IgA. 相似文献