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961.
AIM: To examine the gastrointestinal handling of [1-13C]palmitic acid given as the free acid by measuring the excretion of 13C label in stool in 16 healthy children and 11 patients with cystic fibrosis on their habitual enzyme replacement treatment. METHODS: After an overnight fast, each child ingested 10 mg/kg body weight [1-13C]palmitic acid with a standardised test meal of low natural 13C abundance. A stool sample was collected before the test and all stools were collected thereafter for a period of up to five days. The total enrichment of 13C in stool and the species bearing the 13C label was measured using isotope ratio mass spectrometry. RESULTS: The proportion of administered 13C label excreted in stool was 24.0% (range 10.7-64.9%) in healthy children and only 4.4% (range 1.2-11.6%) in cystic fibrosis patients. The enrichment of 13C in stool was primarily restricted to the species consumed by the subjects (that is as palmitic acid). CONCLUSIONS: There does not appear to be a specific defect in the absorption of [1-13C]palmitic acid in patients with cystic fibrosis. The reasons why cystic fibrosis patients appear to absorb more of this saturated fatty acid than healthy children is not clear and requires further investigation. 相似文献
962.
Alterations in p53 expression are associated with genomic instability,
presumably because loss of p53 leads to an inability to eliminate damaged
and therefore potentially unstable cells by apoptosis or by induced cell
cycle block. We tested this hypothesis by examining the influence of
apoptosis on X-ray-induced chromosome aberration frequency in two isogenic
human B-lymphoblastoid cell lines; TK6, which is sensitive to the induction
of apoptosis, and WI-L2-NS, a p53 mutant resistant to apoptosis induction.
While TK6 was more sensitive than WI- L2-NS cells to the cytotoxic effects
of X-rays, it showed fewer induced chromosome aberrations. Inhibition of
apoptosis in TK6 cells with phorbol 12-myristate 13-acetate (PMA) resulted
in X-ray-induced aberration frequencies similar in magnitude to WI-L2-NS.
The results support the hypothesis that apoptosis acts to selectively
remove damaged cells. The reduction in aberration frequency associated with
apoptosis was seen primarily for unstable types of aberrations; acentric
chromosome fragments and dicentric chromosomes. There was no effect on the
induced frequency of balanced translocations, the stable counterpart to
dicentrics. The failure to remove cells with unstable types of aberrations
is consistent with the genomic instability that accompanies loss of p53
activity.
相似文献
963.
de Vries A; Dolle ME; Broekhof JL; Muller JJ; Kroese ED; van Kreijl CF; Capel PJ; Vijg J; van Steeg H 《Carcinogenesis》1997,18(12):2327-2332
We were interested to study the relationship between DNA lesions, DNA
repair, mutation fixation, and tumour development. Therefore, mice
harbouring lacZ reporter genes and being either wild-type or defective in
the DNA excision repair gene XPA, were treated with the genotoxic
carcinogen benzo[a]pyrene at an oral dose of 13 mg/kg b.w. (3 times/week).
At different time points, i.e. 1, 5, 9 or 13 weeks after start of the oral
administration, levels of BPDE-N2-dG adducts (the major formed DNA adduct
by benzo[a]pyrene in mice), and lacZ mutation frequencies were measured
both in target (spleen) and non-target (lung and liver) tissues. Both in
wild-type and XPA-deficient mice, benzo[a]pyrene treatment resulted in
increased BPDE-N2-dG adduct levels in all three tissues analysed. In
XPA-deficient mice, BPDE-N2-dG adduct levels still increased up to 13 weeks
of oral benzo[a]pyrene treatment, whereas in DNA repair proficient mice
steady-state levels were reached after 5 weeks of treatment. After 13
weeks, the BPDE-N2-dG adduct levels observed in XPA-/- mice, were 2- to
3-fold higher than the steady state levels observed in XPA+/+ mice in the
same tissues. Mutation frequencies in the lacZ reporter gene were the same
in wild- type and XPA-deficient mice that were treated with the solvent
only. Oral benzo[a]pyrene treatment resulted in an increase in mutation
frequency in the lacZ marker gene in all three tissues, but this increase
was most profound in the spleen. After 13 weeks of treatment, a 7-fold
increase in lacZ mutation frequency was detected in the spleen of wild-type
mice as compared to mutation frequencies in control mice. At the same time
point, a 15-fold increase in lacZ mutation frequency was observed in the
spleen of XPA-deficient mice. The data presented here show, that a defect
in NER mainly results in enhanced mutation frequencies in lymphocytic cells
after oral treatment with the genotoxic compound benzo[a]pyrene.
Interestingly, as we established in a previously performed carcinogenicity
assay, the same oral treatment with benzo[a]pyrene induced lymphomas
residing in the spleen of XPA- deficient mice.
相似文献
964.
S Wolkind EM Taylor AJ Waite M Dalton JL Emery 《Acta paediatrica (Oslo, Norway : 1992)》1993,82(11):873-876
Families which had experienced two or more unexpected infant deaths were the subject of detailed confidential enquiries, including necropsy examination. Cases were derived from two main sources: first, deaths occurring during a nationwide programme of support for families with a subsequent baby (8 families) plus 2 families from a scries of confidential enquiries in Sheffield, and second, direct referrals from paediatricians (17 families). Fifty-seven deaths were studied. Twenty-four families had experienced 2 and three had experienced 3 deaths: 11 deaths (19%) were found to be adequately explained by history or post-mortem findings; 7 (12%) were probably accidental; 31 (55%) were most probably due to an action by one of the parents (filicide); only 5 (9%) were considered to be true or idiopathic sudden infant death syndrome; in 3 (5%) cases there was insufficient information to draw a conclusion. Five (18%) of the families lived in circumstances of serious social deprivation. A history of psychiatric illness was present in one or both parents in 18 (67%) of the families. 相似文献
965.
E. A. Shafford J. E. Kingston J. S. Malpas P. N. Plowman J. Pritchard M. O. Savage O. B. Eden 《British journal of cancer》1993,68(6):1199-1204
Testicular function was studied in 40 males treated in childhood for Hodgkin''s disease at St Bartholomew''s Hospital, and the Hospital for Sick Children, London, between 1971-1985. All patients were 16 years or over at evaluation, and off treatment more than 6 years. Basal FSH, LH and testosterone levels were measured. Testicular size was measured using a Prader orchidometer, and all patients were offered a seminal analysis. Twenty-eight patients were treated with chemotherapy, usually ChlVPP. Twenty-one also had radiotherapy, five below the diaphragm. Twelve patients were treated with radiotherapy alone (five below the diaphragm). Twenty-six of 28 patients treated with chemotherapy and three of five patients treated with radiotherapy alone below the diaphragm have elevated basal FSH levels, and 18 of these also have elevated basal LH levels. Median testicular volume is 11 ml (range 5-25 ml). Eleven of 13 patients investigated are azoospermic. All patients have normal testosterone levels, and normal secondary sexual characteristics. There is no biochemical evidence of healing of the damaged germinal epithelium with elevated FSH levels persisting up to 17 years from the end of therapy. These results indicate a high incidence of damage to the germinal epithelium in patients treated with ChlVPP chemotherapy and/or radiotherapy below the diaphragm. Appropriate counselling of these patients with regard to their reproductive capabilities is essential. 相似文献
966.
967.
MR cisternography and myelography with Gd-DTPA in monkeys 总被引:2,自引:0,他引:2
Di Chiro G; Knop RH; Girton ME; Dwyer AJ; Doppman JL; Patronas NJ; Gansow OA; Brechbiel MW; Brooks RA 《Radiology》1985,157(2):373-377
To enhance the contrast between cerebrospinal fluid (CSF), brain, spinal cord, and surrounding meninges and bone on magnetic resonance (MR) images, as well as to study CSF flow, gadolinium-DTPA was injected in the subarachnoid space of eight monkeys. Six doses of progressively higher concentrations (from .125 mmol to 250 mmol) were injected every 30-40 minutes. Images of head and spine were obtained at .26 T or .5 T in sagittal and axial planes, using both spin-echo and inversion-recovery sequences in 13 imaging experiments. Marked, consistent changes of signal intensity in the CSF cavities were observed following the injections. These changes were dose related and occurred at different times in the areas close to the injection site versus those distant, a disparity that obviously was related to CSF flow. Gd-DTPA cisternography and myelography may be valuable in MR imaging of central nervous system disease, such as tumors adjacent to the CSF cavities, abnormal CSF collections (e.g., arachnoidal cysts), CSF rhinorrhea and otorrhea, syringohydromyelia, and studies of hydrocephalus and CSF flow dynamics. 相似文献
968.
969.
Thirty-six women from an original cross-sectional population of 81 were retested after an average time span of 6.1 years to determine the longitudinal effects of aging on aerobic power. Women in their 20s maintained a constant level of VO2max. All other age groups showed a decrease in aerobic power (l . min-1 and ml . kg-1 . min-1) similar to that observed in the cross-sectional study. Although the decline in VO2max was similar for both groups, active women increased walk time on the treadmill, while sedentary women decreased in endurance time. Maximal heart rate also decreased with age but the rate of decrease was not constant across time. HRmax remained relatively steady during the middle years and then declined at a faster rate in the 50- and 60-year-old age groups. The results of the present study suggest that cross-sectional studies can provide valid information about the effect of age on response to maximal exercise provided that close attention is paid to the limitations underlying regression therapy. The data also indicate a need to consider alternatives to linear regression analysis of aging effects, since the rate of change of some variables is not constant across age. 相似文献
970.
S. Levy JL. Tempe A. Aleksijevic C. Giron F. Oberling S. Mayer JM. Lang 《European journal of haematology》1984,33(4):386-390
Natural killer (NK) cell activity of unseparated peripheral blood mononuclear cells from 30 untreated patients with Hodgkin's disease and 22 age- and sex-matched normal controls was evaluated using the classical K 562 cells as targets. A significant defect was demonstrated in the patients with stage I-II and seemed to be more profound in patients with advanced disease (stage III-IV) and in those with B symptoms. The differences between subgroups of patients, however, were not statistically significant, mostly because of the wide dispersion of individual data. Pre-incubation of effector cells with alpha A leucocyte recombinant interferon led to a clear increase in NK cell activity in 4 of 6 patients tested, showing that depressed NK activity in Hodgkin's disease is still susceptible to the enhancing effect of interferon, at least in some patients.— 相似文献