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101.
血管内皮生长因子(VEGF)和可溶性VEGF受体2(sVEGFR-2)由VEGF通路抑制因子所调控,化疗、VEGFR抑制剂或两者联合治疗是否可引起细胞因子和血管生成因子(CAFs)的改变,而这些改变是否又能预示临床获益? 相似文献
102.
C David L. Thomas Paul M. Mayhew Jon Power Kenneth ES Poole Nigel Loveridge John G. Clement Chris J. Burgoyne Jonathan Reeve 《Journal of bone and mineral research》2009,24(11):1808-1818
Hip fracture risk rises 100‐ to 1000‐fold over six decades of age, but only a minor part of this increase is explained by declining BMD. A potentially independent cause of fragility is cortical thinning predisposing to local crushing, in which bone tissue's material disintegrates at the microscopic level when compressed beyond its capacity to maintain integrity. Elastic instability or buckling of a much thinned cortex might alternatively occur under compression. In a buckle, the cortex moves approximately at right angles to the direction of load, thereby distorting its microstructure, eventually to the point of disintegration. By resisting buckling movement, trabecular buttressing would protect the femoral neck cortex against this type of failure but not against crushing. We quantified the effect of aging on trabecular BMD in the femoral neck and assessed its contribution to cortical elastic stability, which determines resistance to buckling. Using CT, we measured ex vivo the distribution of bone in the midfemoral necks of 35 female and 33 male proximal femurs from cases of sudden death in those 20–95 yr of age. We calculated the critical stress σcr, at which the cortex was predicted to buckle locally, from the geometric properties and density of the cortical zone most highly loaded in a sideways fall. Using long‐established engineering principles, we estimated the amount by which stability or buckling resistance was increased by the trabecular bone supporting the most stressed cortical sector in each femoral neck. We repeated these measurements and calculations in an age‐ and sex‐matched series of femoral necks donated by women who had suffered intracapsular hip fracture and controls, using histological measurements of cortical thickness to improve accuracy. With normal aging, trabecular BMD declined asymmetrically, fastest in the supero‐lateral one‐half (in antero‐posterior projection) of the trabecular compartment. When viewed axially with respect to the femoral neck, the most rapid loss of trabecular bone occurred in the posterior part of this region (supero‐posterior [S‐P]), amounting to a 42% reduction in women (34% in men) over five decades of adult age. Because local cortical bone thickness declined comparably, age had no significant effect on the relative contributions of cortical and trabecular bone to elastic stability, and trabecular bone was calculated to contribute 40% (in men) and 43% (in women) to the S‐P cortex of its overall elastic stability. Hip fracture cases had reduced elastic stability compared with age‐matched controls, with a median reduction of 49% or 37%, depending on whether thickness was measured histologically or by CT (pQCT; p < 0.002 for both). This effect was because of reduced cortical thickness and density. Trabecular BMD was similar in hip fracture cases and controls. The capacity of the femur to resist fracture in a sideways fall becomes compromised with normal aging because cortical thickness and trabecular BMD in the most compressed part of the femoral neck both decline substantially. This decline is relatively more rapid than that of femoral neck areal BMD. If elastic instability rather than cortical crushing initiates the fracture event, interventions that increase trabecular bone in the proximal femur have great potential to reduce fracture risk because the gradient defining the increase in elastic stability with increasing trabecular BMD is steep, and most hip fracture cases have sufficient trabecular bone for anabolic therapies to build on. 相似文献
103.
F. P. CARNEIRO A. V. DE MAGALHÃES M. DE JESUS ABREU ALMEIDA COUTO A. L. BOCCA M. I. MUNIZ-JUNQUEIRA & R. N. RIBEIRO SAMPAIO 《Parasite immunology》2009,31(10):646-651
As the diversity in clinical presentation of American tegumentary leishmaniasis (ATL) is determined mainly by the immune response of host, our aim was to evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in lesions of the different clinical forms of ATL. Foxp3+ cells were observed in 39·5% (32/81) of the samples and the number of positive cells was low in all the clinical forms. Even presenting a significantly lower number of CD4+ T cells, diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). In LCL and MCL, the number of Foxp3+ cells correlated positively with the number of apoptotic cells (active caspase-3+ cells). A positive correlation was also observed between the expression of active caspase-3 and FasL in these clinical forms. Our data suggest that increased number of Treg cells may be associated to the hyporesponsiveness observed in DCL and also indicate that the apoptosis may be a possible mechanism of action of Foxp3+ Treg cell in LCL and MCL. However, further studies are required to better understand the mechanism of action of Treg cell. 相似文献
104.
105.
J. D. MASSARO C. E. V. WIEZEL Y. C. N. MUNIZ E. M. REGO L. C. O.
De OLIVEIRA C. T. MENDES‐JUNIOR A. L. SIMÕES 《Haemophilia》2011,17(5):e936-e943
Summary. Hemophilia A is an X‐linked, inherited, bleeding disorder caused by the partial or total inactivity of the coagulation factor VIII (FVIII). Due to difficulties in the direct recognition of the disease‐associated mutation in the F8 gene, indirect diagnosis using polymorphic markers located inside or close to the gene is used as an alternative for determining the segregation of the mutant gene within families and thus for detecting carrier individuals and/or assisting in prenatal diagnosis. This study characterizes the allelic and haplotype frequencies, genetic diversity, population differentiation and linkage disequilibrium of five microsatellites (F8Int1, F8Int13, F8Int22, F8Int25.3 and IKBKG) in samples of healthy individuals from São Paulo, Rio Grande do Sul and Pernambuco and of patients from São Paulo with haemophilia A to determine the degree of informativeness of these microsatellites for diagnostic purposes. The interpopulational diversity parameters highlight the differences among the analyzed population samples. Regional differences in allelic frequencies must be taken into account when conducting indirect diagnosis of haemophilia A. With the exception of IKBKG, all of the microsatellites presented high heterozygosity levels. Using the markers described, diagnosis was possible in 10 of 11 families. The F8Int22, F8Int1, F8Int13, F8Int25.3 and IKBKG microsatellites were informative in seven, six, five and two of the cases, respectively, demonstrating the effectiveness of using these microsatellites in prenatal diagnosis and in carrier identification in the Brazilian population. 相似文献
106.
107.
JE Callender SM Grantham-McGregor SP Walker ES Cooper 《Acta paediatrica (Oslo, Norway : 1992)》1994,83(11):1182-1187
Heavy infection with the geohelminth Trichuris trichiura causes the Trichuris dysentery syndrome (TDS). Growth retardation and anaemia are characteristic of TDS and both are associated with poor development. We have examined the growth and developmental responses to treatment in 19 children aged 27–84 months with TDS. Developmental levels (DQ) were measured with the Griffiths mental development scales. Compared with a control group matched for age, gender and neighbourhood, the TDS children initially had serious deficits in DQ (24 points, p < 0.001). After a year of anthelmintic treatment, the TDS children showed improvement in locomotor development (p < 0.001) compared with the controls. The TDS children also had initial deficits in height-for-age, weight-for-height, mid-upper arm circumference and haemoglobin levels. They caught up rapidly in indices of wasting (weight-for-height and mid-upper arm circumference) and showed steady improvement in height-for-age and haemoglobin levels. Catch-up in height was comparable to that of children recovering from coeliac disease. The importance of continuing prevention after initial treatment is highlighted. 相似文献
108.
胎-母输血综合征对围产儿的影响--附2例报告 总被引:1,自引:0,他引:1
胎-母输血综合征对围产儿的影响——附2例报告丁新黄醒华胎-母输血综合征,即胎儿血液由胎盘的绒毛间隙进入母体血循环,引起胎儿不同程度的失血及母体溶血性输血反应的一组症候群。大量胎-母输血可导致胎儿贫血、休克、死胎、死产;新生儿贫血、休克、死亡。我院在近... 相似文献
109.
The organoselenium compounds benzyl selenocyanate (BSC) and 1,4-
phenylenebis(methylene)selenocyanate (p-XSC), as well as sodium selenite,
are effective chemopreventive agents for various chemically induced tumors
in animal models at both the initiation and postinitiation stages. The
mechanisms involved at the postinitiation stage are not clear. Because
several lines of evidence indicate that inhibition of excess DNA
(cytosine-5)-methyltransferase (Mtase) may be a sufficient factor for the
suppression or reversion of carcinogenesis, we examined the effects of
sodium selenite, BSC, p-XSC and benzyl thiocyanate (BTC), the sulfur analog
of BSC, on Mtase activity in nuclear extracts of human colon carcinomas,
and of p-XSC on the Mtase activity of HCT116 human colon carcinoma cells in
culture. For this purpose, we developed an improved Mtase assay, in which
the incorporation of the methyl-[3H] group from S-adenosyl[methyl-
3H]methionine into deoxycytidine of poly(dI-dC)-poly(dI-dC), is
specifically determined by HPLC with radioflow detection after enzymatic
hydrolysis, enhancing specificity and reliability. In a variation, using
SssI methyltransferase and labeled S- adenosylmethionine, the overall
methylation status of DNA in various tissues can also be compared.
Selenite, BSC and p-XSC inhibited Mtase extracted from a human colon
carcinoma with IC50s of 3.8, 8.1 and 5.2 microM, respectively; BTC had no
effect. p-XSC also inhibited the Mtase activity and growth of human colon
carcinoma HCT116 cells, with an IC50 of approximately 20 microM. The
improved Mtase assay should prove to be a reliable method for screening
potential Mtase inhibitors, especially using cells in culture. We suggest
that inhibition of Mtase may be a major mechanism of chemoprevention by
selenium compounds at the postinitiation stage of carcinogenesis.
相似文献
110.
Enhanced Binding and Degradation of the C1q Subcomponent of Complement by Thioglycollate-Stimulated Guinea Pig Peritoneal Macrophages 总被引:1,自引:0,他引:1
R. VEERHUIS N. KLAR-MOHAMAD L. A. van ES M. R. DAHA 《Scandinavian journal of immunology》1986,23(5):581-587
Expression of C1q receptors on the plasma membrane of thioglycollate-stimulated guinea pig peritoneal exudate macrophages increased 1.54 times as compared to unstimulated controls. A Scatchard plot of the binding of 125I-C1q to the cells revealed that the binding is a result of an increase in the number of receptors and not to an increased affinity of the receptors. Thioglycollate-activated macrophages were found to be 1.6 times more active than nonactivated macrophages in the binding of 125I-C1q at 4 degrees C. The enhanced binding of 125I-C1q by activated peritoneal macrophages was reflected in an increase in the amount of 125I-C1q degraded by these cells as compared to resident peritoneal macrophages. This suggests that stimulation of phagocytic cells leads to an increase in the expression of C1q receptors and to a concomitant increase in the uptake and degradation of C1q. 相似文献