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121.
Lysis of human fibroblast colony-forming cells and endothelial cells by monoclonal antibody (6-19) and complement 总被引:1,自引:0,他引:1
The murine IgG2a monoclonal antibody 6-19 binds to a wide variety of nonhematopoietic cells including human marrow-derived stromal cells but does not bind to marrow or peripheral blood cells. We studied the effects of this antibody and rabbit complement on marrow cells. Fibroblast colonies were eliminated from light density marrow cells by a single incubation with monoclonal antibody 6-19 and complement. The growth and composition of granulocytic and erythroid colonies were unaffected. Specific complement mediated cytotoxicity of the antibody was confirmed on passaged human fibroblasts derived from marrow (more than 99.6% of fibroblasts are killed by a single treatment). Similar results were obtained with human umbilical cord endothelial cells. In addition, such treatment abolished the initiation of Dexter culture stroma. Incubation of bone marrow cell suspensions with this antibody and complement will allow the study of stroma-free marrow cells in long- term liquid cultures. 相似文献
122.
123.
Molecular profiling of tumour budding implicates TGFβ‐mediated epithelial–mesenchymal transition as a therapeutic target in oral squamous cell carcinoma
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124.
染色体脆性位点表达与Ⅱ型糖尿病关系的探讨曾平郭英周迎生一、对象与方法1995年5~12月,我们探讨了染色体脆性位点(fra)的表达与Ⅱ型糖尿病(NIDDM)的关系。实验组为10例老年NIDDM患者,年龄60~69岁,男4例,女6例,2例并发肾病,均有... 相似文献
125.
Recombinant human macrophage colony-stimulating factor (rhM-CSF) was given to cynomolgus monkeys by continuous intravenous infusion or subcutaneous injection, at a dose of 50 to 100 micrograms/kg/d in repetitive 14-day cycles. Starting within 24 to 48 hours of initiation of rhM-CSF, there was a progressive increase in the number of circulating monocytes, from a baseline of 811 +/- 253 cells/microL to a peak of 3,495 +/- 712 cells/microL on day 5 to 7. Many of these cells were large, granular, and extensively vacuolated. The expanded cell population expressed HLA-DR, LFA3, CD11b (904), and CD14 (MY4), and was 77% CD16 (FcRIII) positive by two-color cytofluorometry. In functional assays, fresh monocytes showed little cytotoxicity against cultured human melanoma cells (SKMel-1), with or without prior rhM-CSF treatment. However, after 3 days of in vitro culture in rhM-CSF, monocytes from treated animals mediated efficient antibody-dependent cytotoxicity (ADCC) against SKMel-1 using the murine monoclonal antibody 3F8 (IgG3, anti-ganglioside GD2). Under the same conditions, monocytes from control animals showed little ADCC (17% versus 82%, P less than .05). Antitumor cytotoxicity in the absence of antibody was less efficient and was not significantly different between the two groups. There was a mild decrease in platelet count during rhM-CSF treatment, without clinical symptoms. No abnormalities of serum biochemical parameters were seen. We conclude that parenteral rhM-CSF increases the number of circulating monocytes in nonhuman primates, and that these monocytes mediate increased antitumor ADCC after a brief period of in vitro differentiation. This study has implications for the design of possible future clinical trials combining antitumor monoclonal antibodies and rhM-CSF. 相似文献
126.
127.
A simple approach to prenatal diagnosis of beta-thalassemia in a geographic area where multiple mutations occur 总被引:5,自引:0,他引:5
We describe a simple approach for detecting beta-thalassemia mutations in geographic areas such as southern China where multiple mutations are known to occur. Segments of the beta-globin gene were amplified in vitro by using the polymerase chain reaction. Dot blot hybridization of the amplified DNA with oligonucleotide probes corresponding to the six mutations found in southern China could directly identify the mutations causing beta-thalassemia in the affected families. The increased number of target sequences after amplification allows the use of 35S-labeled probes, which are reusable for up to 3 months. The mutations can be determined in two days. 相似文献
128.
BackgroundChemokines are small molecules that act through G-protein coupled receptors to mediate primarily lymphocyte migration. CXCL16, which interacts with only one receptor (CXCR6), can mediate lymphocyte recruitment and has been implicated in various disease conditions. Steatohepatitis, caused by metabolic syndrome or alcohol misuse, is the commonest cause of liver disease in the UK. We investigated the role of CXCL16 and CXCR6 in the development of steatohepatitis.MethodsExpression of CXCL16 in whole liver and isolated cells was investigated with real-time PCR and immunohistochemistry. Serum and supernatant concentrations of soluble CXCL16 were measured with ELISA. Expression of CXCR6 on lymphocytes was investigated with flow cytometry. Lymphocyte adhesion was assessed with freshly isolated lymphocytes from liver or peripheral blood flowed over confluent layer of isolated human hepatic sinusoidal endothelium (HSEC).FindingsWhole liver expression of CXCL16 was increased relative to normal liver in fatty liver disease with increasing expression seen with increasing steatohepatitis and fibrosis. Immunohistochemistry showed CXCL16 expressed throughout regenerative nodules in both alcoholic and non-alcoholic liver disease. Isolated HSEC, biliary epithelial cells, and hepatoma cell lines increased expression of CXCL16 and released soluble CXCR6 in response to pro-inflammatory cytokines, particularly the combination of tumour necrosis factor α and interferon γ. Peripheral blood lymphocyte CXCR6 expression was confined to CD4 cells; however in the liver CD8+ cells and CD56+ cells more commonly expressed CXCR6. Inhibition of CXCR6 or CXCL16 inhibited transmigration of lymphocytes across HSEC.InterpretationCXCL16 is expressed in diseased liver where it has a role in the transmigration of lymphocytes across endothelium. This may represent a new therapeutic target in liver disease.FundingUK Medical Research Council. 相似文献
129.
Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk 总被引:21,自引:16,他引:21
Ryberg D; Skaug V; Hewer A; Phillips DH; Harries LW; Wolf CR; Ogreid D; Ulvik A; Vu P; Haugen A 《Carcinogenesis》1997,18(7):1285-1289
The A-G polymorphism at codon 104 in the glutathione S-transferase P1
(GSTP1) gene was examined in 138 male lung cancer patients and 297 healthy
controls. The patients had significantly higher frequency of the GG
genotype (15.9%) and a lower frequency of AA (38.4%) than the controls
(9.1% and 51.5%, respectively). The level of hydrophobic DNA- adducts were
determined in lung tissue from 70 current smokers. Patients with the GG
genotype had a significantly higher adduct level than patients with AA
(15.5 +/- 10.2 vs 7.9 +/- 5.1 per 10(8) nucleotides, P = 0.006). We also
analyzed the deletion polymorphism in the GSTM1 gene in 135 male patients
and 342 controls. The patients were stratified according to histology,
smoking dose, age, adduct level and mutational types found in the tumors
(Ki-ras and p53 genes). The results consistently indicated that the GSTM1
null genotype was associated with a slightly increased lung cancer risk.
When the combined GST M1 and P1 genotypes were examined, patients with the
combination null and AG or GG had significantly higher adduct levels than
all other genotype combinations (P = 0.011). The distribution of combined
genotypes was also significantly different in cases and controls, mainly
due to increased frequency of the combination GSTM1 null and GSTP1 AG or GG
among patients.
相似文献
130.
The metabolic activation of tamoxifen and alpha-hydroxytamoxifen to DNA- binding species in rat hepatocytes proceeds via sulphation 总被引:1,自引:1,他引:1
The biotransformation pathway of tamoxifen and alpha-hydroxytamoxifen to
DNA-binding species was investigated in rat hepatocytes in vitro. Rat
hepatocytes were isolated by in situ collagenase perfusion and then
maintained in sulphate-free Dulbecco's modified Eagle's medium. Magnesium
sulphate was added to the medium to give concentrations of 0- 10 microM,
prior to treatment for 18 h with solvent vehicle (DMSO), tamoxifen (10
microM), alpha-hydroxytamoxifen (1 microM) or benzo[a]pyrene (BaP) (10 and
50 microM). DNA was isolated and analysed by 32P-post-labelling. For
tamoxifen and alpha-hydroxytamoxifen, the level of DNA adduct formation was
directly proportional to the concentration of sulphate in the medium.
Between 0 and 10 microM MgSO4, the DNA adduct level increased 10-fold with
both compounds. Rat hepatocytes were also maintained in normal Dulbecco's
modified Eagle's medium and pretreated with
dehydroisoandrosterone-3-sulphate (DHEAS, a sulphotransferase inhibitor) at
concentrations ranging from 0-1 mM, prior to treatment with solvent vehicle
(DMSO), tamoxifen (10 microM), alpha-hydroxytamoxifen (1 microM) or BaP (50
microM). For tamoxifen and alpha-hydroxytamoxifen the level of DNA adducts
was reduced to approximately one-fifth by the addition of DHEAS (0.1 mM).
BaP-DNA adduct formation, which proceeds by a pathway that does not require
sulphation, was not significantly affected by sulphate concentration or by
addition of DHEAS, which demonstrates that the general metabolic capacity
and viability of the hepatocytes were not compromised. It is concluded that
the activation of tamoxifen in rat liver cells to DNA binding products
proceeds predominantly through hydroxylation followed by sulphate ester
formation at the alpha-position of the ethyl side chain.
相似文献