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61.
Slovin SF Ragupathi G Fernandez C Diani M Jefferson MP Wilton A Kelly WK Morris M Solit D Clausen H Livingston P Scher HI 《Cancer immunology, immunotherapy : CII》2007,56(12):1921-1930
We have shown the immunogenicity and safety of synthetic carbohydrate vaccines when conjugated to the carrier keyhole limpet
hemocyanin (KLH) and given with the adjuvant, QS-21, in patients with biochemically relapsed prostate cancer. To determine
whether immune response could be further enhanced with stimulation by multiple antigens, a hexavalent vaccine was prepared
using previously determined doses and administered in a Phase II setting to 30 high-risk patients. The hexavalent vaccine
included GM2, Globo H, Lewisy, glycosylated MUC-1-32mer and Tn and TF in a clustered formation, conjugated to KLH and mixed with QS-21. Eight vaccinations
were administered over 13 months. All 30 patients had significant elevations in antibody titers to at least two of the six
antigens; 22 patients had increased reactivity with FACS. These serologic responses were lower than that seen previously in
patients treated with the respective monovalent vaccines. The reciprocal median combined IgM and IgG antibody titers with
ELISA against MUC1, Tn, TF, globo H and GM2 for these 30 patients were 640, 80, 120, 40 and 0, compared to 1280, 640, 1280,
320 and 160 seen in patients receiving individual monovalent vaccines. This hexavalent vaccine of synthetic “self” antigens
broke immunologic tolerance against two or more antigens in all 30 vaccinated patients, was safe, but antibody titers against
several of the antigens were lower than those seen in individual monovalent trials. No impact on PSA slope was detected. We
address the relevance of the multivalent approach for prostate cancer treatment.
Supported by the Prostate Cancer Foundation, The PepsiCo Foundation, The Sharon Hels and Brad Reed Fund, Swim Across America,
The Sara Chait Foundation.
Dr. Philip Livingston is a consultant for and shareholder in Progenics Pharmaceuticals, Inc. 相似文献
62.
Improved immunocytochemical detection of daunomycin 总被引:3,自引:3,他引:0
Improved immunocytochemical (ICC) detection of the anthracycline anticancer antibiotic daunomycin (DM) has been achieved by
use of hydrogen peroxide oxidation prior to ICC staining for DM. The new method greatly enhanced the localization of DM accumulation
in cardiac, smooth and skeletal muscle of rats after a single i.v. dose of the drug. DM accumulated in the nuclei as well
as in the sarcoplasm, where it occurred in the form of small granules, which were particularly evident in cardiac muscle cells.
The distribution of the granules coincided with that of mitochondria. Uptake of DM in nuclei and mitochondria of heart muscle
cells may help to improve our understanding of the cardiac toxicity of DM and related anthracyclin antibiotics. A number of
ELISA tests were carried out in order to elucidate the mechanims of H2O2−assisted antigen retrieval. A possible mechanism is that DM is reduced and converted to its semiquinone and/or hydroquinone
derivative in vivo. Oxidation by hydrogen peroxide acts to convert these derivatives back to the native antigen. The improved
ICC methodology using oxidation to recreate native antigens from reduced metabolites may be helpful also with respect to the
localization of other drugs. 相似文献
63.
《Cytokine》2015,76(2):256-260
SREC-I is a class F scavenger receptor with key role in the immune response, particularly in antigen presenting cell (APC) such as macrophages and dendritic cells (DC). This receptor is able to mediate engulfment of dead cells as well as endocytosis of heat shock protein (HSP)–antigen complexes. SREC-I could thus potentially mediate the tolerizing influence of apoptotic cells or the immunostimulatory effects of HSP–peptide complexes, depending on context. This receptor was able to mediate presentation of external antigens, bound to HSPs through both the class II pathway as well as cross presentation via MHC class I complexes. In addition to its recently established role in adaptive immunity, emerging studies are indicating a broad role in innate immunity and regulation of cell signaling through Toll Like Receptors (TLR). SREC-I may thus play a key role in APC function by coordinating immune responses to internal and external antigens in APC. 相似文献
64.
Park JH Nam Y Park SY Kim JK Choe NH Lee JY Oh YS Suh JG 《Journal of biochemical and molecular toxicology》2011,25(4):238-243
High glucose levels induce cell death in many cell types, including pancreatic β-cells. Although protective agents against glucotoxicity have been searched for extensively, so far none have been found. In this report, we tested silk fibroin (SF) as a candidate material for antiglucotoxicity in the pancreatic β-cell (HIT-T15 cell) line. Approximately 50% of cells were killed after treatment with 80 mg/mL glucose. This reduction of cell number was recovered by the addition of SF at 50 mg/mL. SF treatment also decreased cellular reactive oxygen species (ROS) and increased proliferating cellular nuclear antigen (PCNA) immunoreactivity. In addition, TUNEL assays demonstrated that SF protects against glucose-induced apoptosis of HIT-T15 cells, suggesting that SF might protect cells from cell death by lowering cellular ROS levels. SF also induced expression of the insulin-like growth factor-1 (IGF-1) gene, and IGF-1 expression may be the cause of SF-induced protection against glucose toxicity. Taken together, these results suggest that SF could serve as a potential therapeutic agent to treat the hyperglycemia-induced death of pancreatic β-cells. 相似文献
65.
目的:探索一种简单有效的行BrdU免疫组织化学染色抗原热修复的方法。方法:本实验探索了三种抗原热修复方法:1)漂片煮沸法,2)贴片煮沸法,3)贴片改良法。将贴有冰冻组织切片的玻片置于恒温封闭体系中进行热修复。之后行BrdU免疫组化染色,栗集图像对这三种热修复方法进行比较。针对贴片改良法行BrdU与NeuN、P。CERB和DCX的荧光双标,采集图像以观察该方法在免疫荧光甄标实验中应用的可行性。结果:1)漂片煮沸法脑组织切片在经过热修复处理后,切片卷起皱缩,不能进行后续实验步骤;2)贴片煮沸法可见少量BrdU阳性细胞,但背景深,且少数脑片起泡,假阳性现象严重;3)贴片改良法B-U免疫组化及与NeuN、P-CERB和DCX的免疫荧光双标染色背景浅,阳性细胞明显。结论:采用改良的热修复法能充分暴露BrdU抗原,DAB显色及免疫荧光染色结果理想。此方法为一种较好的行BrdU免疫组织化学染色抗原热修复方法。 相似文献
66.
The antigen-2 or proline rich antigen (Ag2/PRA) from Coccidioides immitis, known to protect mice against experimental Coccidioidomycosis, was expressed in the genetically attenuated cholera vaccine candidate Vibrio cholerae 638 and its thymine auxotrophic derivative 638T. Intranasal immunization of mice with strains producing Ag2/PRA induced serum vibriocidal antibody and Ag2/PRA-specific total IgG responses in outbred Swiss Webster and inbred BALB/c mice. Analysis of IgG subclasses showed a predominance of IgG2a subclass antibodies. Lymphocytes from immunized mice stimulated with pure Ag2/PRA showed a significant proliferative response with production of interferon-gamma. Positive selection for plasmid maintenance in vivo did not enhance immune response to Ag2/PRA. These results demonstrate that genetically attenuated strains of the non-invasive pathogen V. cholerae can be used to express and deliver foreign antigens to stimulate a Th1 type of immune response. 相似文献
67.
68.
Reduction of apoptosis through the mitochondrial pathway by the administration of acetyl-L-carnitine to mouse fibroblasts in culture 总被引:1,自引:0,他引:1
It is shown in literature that stress, such as deprivation of trophic factors and hypoxia, induces apoptosis in cultured cells and in tissues. In light of these results, we explored the possibility of protecting cells from programmed death by improving the metabolism of the mitochondrion. To this end, acetyl-L-carnitine was administered at various concentrations under conditions of serum deprivation. The choice of this drug was based on the accepted notion that acetyl-L-carnitine is able to stabilize mitochondrial membranes and to increase the supply of energy to the organelle. The results presented here indicate that the drug protects cells from apoptotic death: this is demonstrated by a lower positivity to the TUNEL reaction and by a strong reduction of the apoptotic DNA ladder in serum-deprived cells. The involvement of the mitochondrial apoptotic pathway was assessed by cytochrome C release and immunoreactivity to caspase 3. Moreover, acetyl-L-carnitine stimulates cell proliferation. 相似文献
69.
Villavedra M McCarthy K To J Morrison R Crosbie P Broady K Raison RL 《International journal for parasitology》2005,35(13):1417-1423
Amoebic gill disease (AGD), the most serious infectious disease affecting farmed salmon in Tasmania, is caused by free-living marine amoeba Neoparamoeba sp. The parasites on the gills induce proliferation of epithelial cells initiating a hyperplastic response and reducing the surface area available for gaseous exchange. AGD can be induced in salmon by exposure to freshly isolated Neoparamoeba from AGD infected fish, however cultured Neoparamoeba are non-infective. We describe here antigenic differences between freshly isolated and in vitro cultured parasites, and within individual isolates of the parasite cultured under different conditions. Immunoblot analysis using polyclonal antisera, revealed differences in the antigen profiles of two cultured isolates of Neoparamoeba sp. when they were grown on agar versus in liquid medium. However, the antigen profiles of the two isolates were very similar when they were grown under the same culture conditions. Comparison of these antigen profiles with a preparation from parasites freshly isolated from infected gills revealed a very limited number of shared antigens. In addition monoclonal antibodies (mAbs) raised against surface antigens of cultured parasites were used in an indirect immunofluorescence assay to assess the expression of specific surface antigens of Neoparamoeba sp. after various periods in culture. Significant changes in antigen expression of freshly isolated parasites were observed after 15 days of in vitro culture. The use of mAb demonstrated progressive exposure/expression of individual antigens on the surface of the freshly isolated parasites during the period in culture. 相似文献
70.
Mutations in transporters associated with antigen processing (TAP-1 and -2) required for the transport of cytosolic endogenous peptides to the endoplasmic reticulum correlate with increased metastatic potential and reduced host survival in several malignancies. To address the possible function of TAP as a "tumor suppressor" gene, we show that correction of TAP-1 and/or TAP-2 defects in B16 mouse melanoma enhanced the cell surface expression of MHC class I molecules and significantly reduced the rate of subcutaneous tumor growth and pulmonary metastatic burden. Cytotoxic assays confirmed increased sensitivity of TAP-1 and/or TAP-2 transfected clones of B16 melanoma to cytotoxic T lymphocytes. These results indicate that the expression of TAP limits the malignant potential of tumors with implications for CD8(+) T cell-based immunotherapy in controlling growth of certain TAP-deficient malignancies. 相似文献