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排序方式: 共有580条查询结果,搜索用时 15 毫秒
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2.
Riitta Mustonen Eivor Elovaara Antti Zitting Kaija Linnainmaa Harri Vainio 《Archives of toxicology》1989,63(3):203-208
The induction of hepatic peroxisome proliferation and drug metabolizing enzymes and of sister chromatid exchange (SCE) in lymphocytes was studied in male Han/Wistar rats after exposing them for 2 weeks to a commercial chlorophenolate formulation (Ky-5) (100mg/kg/ day), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; 0.05–5 g/kg/wk) and to the pure phenoxyacetic acids, 2,4-dichlorophenoxyacetic acid (2,4-D; 100 mg/kg/day) and 2-chloro-4-methylphenoxyacetic acid (MCPA; 100 mg/kg/day). The chlorophenolate formulation and pure 2,4-D and MCPA caused significant increases in the number of peroxisomes in liver cells, although the average size of peroxisomes was not affected, whereas the effect of even the highest dose of 2,3,7,8-TCDD remained small. This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate. The relative weight of the liver increased significantly in rats treated with the chlorophenolate formulation and with 2,3,7,8-TCDD (5.0 and 0.5 g/kg). The pattern of induction of xenobiotic metabolizing enzymes showed some differences between chlorophenolate treatment and 2,3,7,8-TCDD treatment. Furthermore, the effects of pure phenoxyacetic acids were different from that seen with chlorophenolate and 2,3,7,8-TCDD. The highest dose of 2,3,7,8-TCDD increased the frequency of SCE in circulating lymphocytes slightly, but significantly. 相似文献
3.
Immunochemical characterization of cytochrome P-450 isozymes responsible for benzene oxidation in the rat liver 总被引:4,自引:0,他引:4
Nakajima Tamie; Elovaara Eivor; Park Sang S.; Gelboin Harry V.; Hietanen Eino; Vainio Hani 《Carcinogenesis》1989,10(9):1713-1717
The contribution of cytochrome P-450 isozymes to benzene metabolismin liver microsomes from fed, fasted, pyrazole-, pbenobarbital(PB)- and ethanol-treated rats and in respective isocaloriccontrols was investigated using monoclonal antibodies (mAbs).Clone 1-7-1 mAb did not inhibit benzene metabolism, whereasclone 2-66-3 inhibited only in PB-induced microsomes at a highconcentration of benzene (6.26 mM), and clone 1-91-3 mAb inhibitedbenzene metabolism in all cases. The degree of inhibition wasas follows: fed isocaloric control PB < fasted < pyrazole ethanol. The pattern of inhibition was similar with clone 1-91-3for low (0.23 mM) and high concentrations of benzene, exceptin PB-induced mkrosomes. Western blot analysis showed that clone1-7-1 mAb did not bind any liver mkrosomal protein in the regionof cytochrome P-450s, whereas with clone 2-66-3 a clear-cutband was seen only in liver microsomes from PB-treated rats,with clone 1-98-1, a band was detected in mkrosomes from alltreated groups, in the following order: PB = isocaloric control< fed < fasted < pyrazole < ethanol. These resultsindicate that (i) cytochromes P-450b,e and P-450J contributeto benzene metabolism in rat liver; (ii) the former has a lowaffinity to benzene and is induced by PB; and (iii) P-450J hasa high affinity to benzene and is induced by 1-day fasting,pyrazole and ethanol, but decreased by PB treatment. 相似文献
4.
A mouse model for alpha-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids 总被引:2,自引:0,他引:2
Savolainen K Kotti TJ Schmitz W Savolainen TI Sormunen RT Ilves M Vainio SJ Conzelmann E Hiltunen JK 《Human molecular genetics》2004,13(9):955-965
alpha-Methylacyl-CoA racemase (Amacr) deficiency in humans leads to sensory motor neuronal and liver abnormalities. The disorder is recessively inherited and caused by mutations in the AMACR gene, which encodes Amacr, an enzyme presumed to be essential for bile acid synthesis and to participate in the degradation of methyl-branched fatty acids. To generate a model to study the pathophysiology in Amacr deficiency we inactivated the mouse Amacr gene. As per human Amacr deficiency, the Amacr(-/-) mice showed accumulation (44-fold) of C27 bile acid precursors and decreased (over 50%) primary (C24) bile acids in bile, serum and liver, however the Amacr(-/-) mice were clinically symptomless. Real-time quantitative PCR analysis showed that, among other responses, the level of mRNA for peroxisomal multifunctional enzyme type 1 (pMFE-1) was increased 3-fold in Amacr(-/-) mice. This enzyme can be placed, together with CYP3A11 and CYP46A1, to make an Amacr-independent pathway for the generation of C24 bile acids. Exposure of Amacr(-/-) mice to a diet supplemented with phytol, a source for branched-chain fatty acids, triggered the development of a disease state with liver manifestations, redefining the physiological significance of Amacr. Amacr is indispensable for the detoxification of dietary methyl-branched lipids and, although it contributes normally to bile acid synthesis from cholesterol, the putative pMFE-1-mediated cholesterol degradation can provide for generation of bile acids, allowing survival without Amacr. Based upon our mouse model, we propose elimination of phytol from the diet of patients suffering from Amacr deficiency. 相似文献
5.
C. Sandler E. Ekokoski K. A. Lindstedt P. J. Vainio M. Finel T. Sorsa P. T. Kovanen L. M. Golub K. K. Eklund 《Inflammation research》2005,54(7):304-312
Objective: To find novel inhibitors of mast cell function we have studied the effect of a potent, non-antimicrobial, chemically modified tetracycline, CMT-3 or COL-3, on key functions of mast cells.Methods and Results: In the presence of 25 μM CMT-3, the 48/80-induced histamine release from rat serosal mast cells was inhibited significantly, to 43.0 ± 7.3% of control. Similarily, the activation-induced secretion of TNF-α and IL-8 by HMC-1 cells were decreased in the presence of 25 μM CMT-3 to 13.5 ± 4.1% and 9.7 ± 1.1% of control, respectively. CMT-3 did not cause intracellular accumulation of TNF-α but instead it reduced the expression of TNF-α mRNA in HMC-1 cells. Moreover, CMT-3 was found to significantly inhibit the protein kinase C (PKC) activity with IC50 value of 31 μM. CMT-3 inhibited effectively both human recombinant PKCalpha and PKCdelta isoforms. In comparison to doxycycline, CMT-3 was more effective as an inhibitor of both cytokine production and PKC activity.Conclusions: Considering the central role of PKC in mast cell activation, PKC inhibition could, at least partially, explain the observed inhibitory effects of CMT-3. The inhibition of the key proinflammatory functions of mast cells by CMT-3 suggests its potential clinical usefulness in the treatment of allergic and inflammatory disorders.Received 18 February 2005; returned for revision 7 March 2005; accepted by A. Falus 21 April 2005 相似文献
6.
Ontogeny of alloreactivity in the chicken thymus and spleen was studied in mixed lymphocyte cultures. Mixed lymphocyte reaction (MLR) to total major histocompatibility complex (MHC) (B-complex in chicken) disparity was first detected in the thymus of 16-day-old embryo and regularly detectable from the 18th embryonal day on. Small strain-specific differences in the strength and appearance of the response were, however, observed. MLR to class I MHC (B-F) antigen disparity was not detectable before hatching. Exogenous interleukin-2-containing supernatant added to the cultures had only a minor effect on MLR of embryonal thymocytes. In the spleen, MLR was first detectable in some strain combinations on day 3 and regularly found on the 7th day posthatching, indicating colonization of peripheral lymphoid organs by thymus-derived mature T cells. Our results show the association of phenotypic and functional maturation of chicken T cells. The ontogeny of alloreactivity can now be compared to the appearance of T cell receptor (TCR), CD4, and CD8-bearing cells in the thymus and peripheral lymphoid organs. 相似文献
7.
8.
O Lassila A Alanen O Vainio E Houssaint J R Pink W T Weber 《European journal of immunology》1988,18(11):1867-1870
To determine the presence of precursor B cells in chick embryos surgically bursectomized at 72 h of incubation (E-Bx) we studied chick chimeras that were produced by establishing parabiotic connections between blood vessels of chorioallantoic membranes of normal and surgically bursectomized chick embryos. Using sex chromosomes and a B cell alloantigen (Bu-1a) as markers we showed that chick embryos bursectomized at 72 h of incubation contain B cell precursors capable of colonizing the bursa of Fabricius and developing into B lymphocytes. The repopulation capacity of 14-day-old embryonic spleen cells from E-Bx recipients was tested by transferring them into age-matched X-irradiated Bu-1-disparate embryos. The results show that B cell precursors are present in 14-day spleen of chick embryos bursectomized at 72 h of incubation. These precursors carry the Bu-1 B cell alloantigen, suggesting that commitment to the B cell lineage can take place in the absence of bursa. 相似文献
9.
Promise of molecular epidemiology--epidemiologic reasoning, biological rationale and risk assessment
Vainio H 《Scandinavian journal of work, environment & health》1999,25(6):498-504
Molecular epidemiology has emerged as a natural outgrowth of attempts to apply information derived from the explosion in molecular biology to disease in human populations. The incorporation of biomarkers into classical epidemiologic designs holds the promise of unraveling mechanisms, elucidating gene-environment interactions, and dissecting heterogeneity. The primary interest of molecular epidemiology is in the identification of factors in the physical and social environment which affect the risk for disease and which are amenable to preventive intervention. The explosion in molecular technology has not, however, resulted in radical, widespread improvements in epidemiologic results and therefore has led to a sense of frustration in the public health community. As experience accumulates, there is new appreciation that attention to study design, infrastructure, and biomarker validation can improve the results. 相似文献
10.
A prospective study of body size in different periods of life and risk of premenopausal breast cancer. 总被引:5,自引:0,他引:5
Elisabete Weiderpass Tonje Braaten Cecilia Magnusson Merethe Kumle Harri Vainio Eiliv Lund Hans-Olov Adami 《Cancer epidemiology, biomarkers & prevention》2004,13(7):1121-1127
The prevalence of obesity at all ages is increasing epidemically worldwide. Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce. In 1991 to 1992, a prospective cohort study was assembled in Norway and Sweden. We included in the analysis presented here 99,717 premenopausal women. During the follow-up period, which ended in December 1999, 733 of these women developed a primary invasive breast cancer. Overweight and obesity [body mass index (BMI) > 25 kg/m(2)] at enrollment was associated with a decreased risk of premenopausal breast cancer (P for linear trend = 0.007). Apparent associations between perceived body shape at age 7 and BMI at age 18, with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk, lost their statistical significance after adjustment for BMI at cohort enrollment. Body size at age 7 was correlated with BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48). Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk. Height was related to risk, with a statistically significantly 30% reduced risk only in women shorter than 160 cm as compared with taller ones. The decreased risk of premenopausal breast cancer was observed in overweight and obese women without, but not in those with, a family history of breast cancer. 相似文献