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1.
Verschuren MC; Blom B; Bogers AJ; Spits H; van Dongen JJ 《International immunology》1998,10(12):1873-1880
Recombination of deltaRec to psiJalpha will delete the TCR delta gene,
which is thought to play an important role in the bifurcation of the TCR
alphabeta versus TCR gammadelta differentiation lineages. We recently
detected a DNA-binding protein in human thymocytes, the so- called PJA-BP,
which recognizes the psiJalpha gene segment and might be one of the factors
involved in the regulation of preferential deltaRec- psiJalpha
rearrangements. We now investigate PJA-BP expression and its correlation
with TCR delta gene deletion in thymocytes. Our electrophoretic mobility
shift assay experiments showed that the PJA-BP is evolutionary conserved in
human, murine and simian thymocytes. Using a large series of human
hematopoietic malignancies (n = 30), we conclude that PJA-BP expression is
thymocyte specific and seems to be restricted to thymocytes committed to
the TCR alphabeta lineage. Analysis of seven well-defined human thymocyte
subpopulations showed that preferential deltaRec-psiJalpha rearrangements
as well as PJA-BP expression can be detected from the immature
CD34-/CD1+/CD3- /CD4+/CD8alpha+beta- thymocyte differentiation stage
onwards. These experiments indicate that expression of PJA-BP in human
thymocytes starts simultaneously with preferential deltaRec-psiJalpha
rearrangements, which supports our hypothesis that PJA-BP is one of the
factors involved in the preferential recombination of deltaRec to
psiJalpha.
相似文献
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Frank Miedema Pedro A. T. Tetteroo Wim G. Hesselink Guy Werner Hergen Spits Cornelis J. M. Melief 《European journal of immunology》1984,14(6):518-523
A monoclonal antibody, designated CLB-LFA-1/1, directed to the human lymphocyte-function-associated antigen 1 (LFA-1) was raised by immunization of mice with the peripheral blood lymphocytes of a Tγ lymphocytosis patient. The monoclonal antibody was selected by inhibition of the natural killer cell and the antibody-dependent killer cell activity of the patient's Tγ lymphocytes. In addition, the monoclonal antibody was shown to inhibit the cytotoxic activity of T cell clones specific for either class I or class II HLA molecules. The antigen recognized by CLB-LFA-1/1 consisted of three polypeptide chains with molecular weights of 180000 (α), 155000 and 94000 (β). The antibody reacted with T cells, B cells, monocytes and granulocytes, and stained normal Tγ cells and Tγ cells of patients with Tγ lymphocytosis two- to threefold stronger than normal T cells. It was shown that LFA-1 and the Fc receptor on Tγ cells did not comodulate and it is therefore concluded that Fc receptors and LFA-1 are independent membrane structures, both required for the killer cell activity of Tγ cells. 相似文献
4.
Rosalie M Luiten Esther W M Kueter Wolter Mooi Maarten P W Gallee Elaine M Rankin Winald R Gerritsen Shirley M Clift Willem J Nooijen Pauline Weder Willeke F van de Kasteele Johan Sein Paul C M van den Berk Omgo E Nieweg Anton M Berns Hergen Spits Gijsbert C de Gast 《Journal of clinical oncology》2005,23(35):8978-8991
PURPOSE: To determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients. PATIENTS AND METHODS: Sixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays. RESULTS: The high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1- or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1- and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-gamma on specific antigenic stimulation. CONCLUSION: We conclude that vaccination with GM-CSF-transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation. 相似文献
5.
Dominika Dziedzicka Christina Markouli Lise Barbé Claudia Spits Karen Sermon Mieke Geens 《Stem cell reviews》2016,12(6):721-730
When aiming for homogenous embryoid body (EB) differentiation, the use of equal-sized EBs is required to avoid a size-induced differentiation bias. In this study we developed an efficient and standardized EB formation protocol for human pluripotent stem cells (hPSC) cultured in a laminin-521-based xeno-free system. As the cell proliferation rate of the cells growing on laminin-521 strongly affected the efficiency of aggregate formation, we found that recently passaged cells, as well as the addition of ROCK inhibitor, were essential for reproducible EB formation from hPSC single-cell suspensions. EBs could be obtained in a variety of differentiation media, in 96-well round-bottom plates and in hanging drops. Gene expression studies on differentially sized EBs from three individual human embryonic stem cell lines demonstrated that the medium used for differentiation influenced the differentiation outcome to a much greater extent than the number of cells used for the initial EB formation. Our findings give a new insight into factors that influence the EB formation and differentiation process. This optimized method allows us to easily manipulate EB formation and provide an excellent starting point for downstream EB-based differentiation protocols. 相似文献
6.
7.
C-reactive protein and coronary heart disease in western Turkey 总被引:9,自引:0,他引:9
Onat A Sansoy V Yildirim B Keleş I Uysal O Hergenç G 《The American journal of cardiology》2001,88(6):601-607
C-reactive protein (CRP) has been recognized as a useful marker for coronary or cardiovascular risk in healthy subjects or patients with coronary heart disease (CHD) in industrialized societies. We assessed whether CRP could serve as a marker of prevalent CHD risk in a cross-sectional study of a population with low cholesterol levels (4.61 mmol/L in men and 4.82 mmol/L in women) but higher prevalence of other risk factors. In 1,046 participants of the Turkish Adult Risk Factor Survey in 2000, high-sensitivity CRP as well as other risk variables were evaluated, and CHD was diagnosed, based on clinical findings and Minnesota coding of electrocardiograms at rest. Almost an equal number of men and women > or = 30 years of age constituted the population sample of the western regions of Turkey. Geometric mean value of CRP was 1.9 mg/L (interquartile range 0.8 to 4.3), without revealing a significant difference in gender. CRP was correlated with many variables, notably those involving central obesity, fibrinogen, and apolipoprotein-B, but not with smoking status (regardless of age adjustment). In multiple regression models, blood fibrinogen, waist circumference, total cholesterol, and physical activity grade were independently associated with log CRP concentrations. Among many risk variables, CRP quartiles and systolic blood pressure were, besides age and gender, the only significant independent determinants of CHD. The age-adjusted odds ratio for CHD in the highest as opposed to the lowest quartile was 4.48 (p < 0.001). Even after adjustment for the 5 previously mentioned determinants of CRP, a 4.2-fold increased risk of CHD still persisted between the highest and lowest quartiles. Thus, the observed increased risk was not in large part due to the intermediary effects of fibrinogen, nor were some indicators of insulin resistance, but interaction appeared to be independent of these effects. Thus, CRP values serve as a marker of prevalent CHD risk in populations with low cholesterol levels. This association is independent of, or in addition to, the effects of conventional risk factors, suggesting that the contribution of chronic low-grade inflammation to the atherothrombotic process is present even in the setting of low cholesterol levels. 相似文献
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9.
Genomic organization of the human T-cell antigen-receptor alpha/delta locus. 总被引:13,自引:2,他引:13 下载免费PDF全文
10.
Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins 下载免费PDF全文
Alfred H. Schinkel Ulrich Mayer Els Wagenaar Carla A. A. M. Mol Liesbeth van Deemter Jaap J. M. Smit Martin A. van der Valk Arie C. Voordouw Hergen Spits Olaf van Tellingen J. Mark J. M. Zijlmans Willem E. Fibbe Piet Borst 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(8):4028-4033
The mdr1-type P-glycoproteins (P-gps) confer multidrug resistance to cancer cells by active extrusion of a wide range of drugs from the cell. To study their physiological roles, we have generated mice genetically deficient in the mdr1b gene [mdr1b (−/−) mice] and in both the mdr1a and mdr1b genes [mdr1a/1b (−/−) mice]. In spite of the host of functions speculatively attributed to the mdr1-type P-gps, we found no physiological abnormalities in either strain. Viability, fertility, and a range of histological, hematological, serum–chemical, and immunological parameters were not abnormal in mdr1a/1b (−/−) mice. The high level of mdr1b P-gp normally present in the pregnant uterus did not protect fetuses from a drug (digoxin) in the bloodstream of the mother, although the protein did reduce drug accumulation in the adrenal gland and ovaries. Pharmacologically, mdr1a/1b (−/−) mice behaved similarly to the previously analyzed mdr1a (−/−) mice, displaying, for instance, increased brain penetration and reduced elimination of digoxin. However, both mdr1a and mdr1b P-gps contributed to the extrusion of rhodamine from hematopoietic progenitor cells, suggesting a potential role for the endogenous mdr1-type P-gps in protection of bone marrow against cytotoxic anticancer drugs. This, and the normal viability of mdr1a/1b (−/−) mice, has implications for the use of P-gp-blocking agents in cancer and other chemotherapy. mdr1a/1b (−/−) mice should provide a useful model system to further test the pharmacological roles of the drug-transporting P-gps and to analyze the specificity and effectivity of P-gp-blocking drugs. 相似文献