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Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4 总被引:4,自引:0,他引:4
Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci. 相似文献
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C B Hu E Y Lee J E Hewitt J U Baenziger J Z Mu K DeSchryver-Kecskemeti D H Alpers 《Gastroenterology》1991,101(6):1477-1487
Because specific uptake of the asialoglycoprotein haptocorrin has been reported in suckling distal intestine, evidence of the asialoglycoprotein receptor in rat ileum was sought. On Western blot, two different polyclonal antisera against purified rat holoreceptor recognized only proteins of the size of the minor receptor components (51 and 55 kilodaltons) in both suckling and adult rat intestine. Messenger RNA encoding the minor component (RHL-2/3) was detected in total RNA extracted from rat ileum. Calcium-specific binding of porcine or rat haptocorrin-[57Co]cobalamin complexes was detected in the brush border membranes of distal suckling rat and porcine small intestine. This binding was almost completely blocked by another asialoglycoprotein, asialofetuin. The pH optimum for binding was 6-9, with a Ka of 0.25 nmol/L and a capacity of 4.6 fmol/mg protein. These properties, with the exception of the low capacity, are all consistent with those of the intact receptor on hepatocytes. The intestinal receptor was localized not to the basolateral membrane, as in the liver, but to the apical brush border, as suggested by the binding data. Furthermore, immunoperoxidase stains of paraffin-embedded tissue detected strong binding to the brush border and apical phagolysosome of mid and distal suckling rat intestine. These data show that, contrary to expectations, the minor components of the asialoglycoprotein receptor are functional and expressed in the apical membrane of the suckling intestine. The abundance of the protein by Western blot suggests possible roles for it in the neonatal gut other than haptocorrin binding. 相似文献
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Determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease: The DOC study 下载免费PDF全文
Sarah J. Ronaldson MSc BSc Lisa Dyson MSc BA Laura Clark MSc BSc Catherine E. Hewitt PhD MSc BSc David J. Torgerson PhD MSc Brendan G. Cooper PhD MSc BSc Matt Kearney MPH MB ChB William Laughey MBChB MSc Raghu Raghunath PhD MD Lisa Steele BSc Rebecca Rhodes BMED Sci Joy Adamson PhD MSc BSc 《Journal of evaluation in clinical practice》2018,24(3):487-495
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Benjamin W. Dean Sarah N. Hewitt Morgan C. Begos Angela Gomez Locksley L. McV. Messam 《Transfusion and apheresis science》2018,57(1):40-45
Objectives
To estimate the associations of nationality, university program, donation history and gender, with blood donation barriers experienced by non-donating students on the day of a campus blood drive. This project focused particularly on nationality and the effect of the different blood donation cultures in the students' countries of origin.Methods
A retrospective cohort study of 398 North American and Caribbean university students was conducted at St. George's University, Grenada, in 2010. Data were collected from non-donating students on campus while a blood drive was taking place. Log-binomial regression was used to estimate associations between the exposures of interest and donation barriers experienced by the students.Results
North American (voluntary blood donation culture) students were more likely than Caribbean (replacement blood donation culture) students to experience “Lack of Time” (relative risk (RR)?=?1.57; 95% confidence interval (CI): 1.19–2.07) and “Lack of Eligibility” (RR?=?1.55; 95% CI: 1.08–2.22) as barriers to donation. Conversely, Caribbean students were a third as likely to state “Lack of Incentive” (RR?=?0.32; 95% CI: 0.20–0.50), “Fear of Infection” (RR?=?0.35; 95% CI: 0.21–0.58), and “Fear of Needles” (RR?=?0.32; 95% CI: 0.21–0.48) were barriers than North American students.Conclusions
University students from voluntary blood donation cultures are likely to experience different barriers to donation than those from replacement cultures. Knowledge of barriers that students from contrasting blood donation systems face provides valuable information for blood drive promotion in university student populations that contain multiple nationalities. 相似文献59.
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