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101.
102.
The cell type of origin of primary mouse lung tumors was investigated histochemically. Succinate dehydrogenase (SDH) histochemistry readily differentiated bronchiolar epithelial (Clara and ciliated) cells from alveolar type II pneumocytes in mice aged 10 days through adult. Correspondingly, freshly-isolated Clara cells stained intensely but type II cells did not. Urethane-induced papillary adenomas exhibited intense SDH staining while alveolar adenomas stained very lightly. The relative SDH activities of these two types of pulmonary adenomas is consistent with the hypothesis that alveolar tumors arise from type II pneumocytes and papillary tumors from Clara cells.  相似文献   
103.
Metabolism of the antioxidant butylated hydroxytoluene (BHT; 2,6-di-tert-butyl-4-methylphenol) has been studied with liver and lung microsomes from rats and mice. The structures of several previously reported metabolites were confirmed, the identities of four new metabolites were determined, pathways of oxidation were investigated, and quantitative data were obtained for several of the products. Two main metabolic processes occur, hydroxylation of alkyl substituents and oxidation of the aromatic pi electron system. The former leads to the 4-hydroxymethyl product (BHT-BzOH) and a primary alcohol resulting from hydroxylation of a t-butyl group (BHT-tBuOH). Additional metabolites were produced by oxidation of BHT-BzOH to the corresponding benzaldehyde and benzoic acid derivatives. Hydroxylation of BHT-tBuOH occurs at the benzylic methyl position, and the resulting diol is oxidized further to the hydroxybenzaldehyde derivative. Oxidation of the pi system leads to the quinol, 2,6-di-t-butyl-4-hydroxy-4-methyl-2,5-cyclohexadienone, the quinone, 2,6-di-t-butyl-4-benzoquinone, and the quinone methide, 2,6-di-t-butyl-4-methylene-2,5-cyclohexadienone. Derivatives of the quinol and quinone with a hydroxylated t-butyl group were also formed. Quantitative data demonstrate that BHT-BzOH is the principal metabolite in rat liver and lung microsomes. On the other hand, mice produce large amounts of both BHT-BzOH and BHT-tBuOH in these tissues. The metabolite profile was similar in rat liver and lung. Mouse lung, however, produced more quinone relative to other metabolites than mouse liver.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
104.
Summary Monospecific antibodies were prepared by nitrocellulose blot immunoaffinity to 3 polypeptide components of the host-membrane associated B antigen of Marek's disease herpesvirus (MDV) and to its soluble A antigen. The B antigen comprised a 200 kDa dimer which is 2-mercaptoethanol (2-ME) labile, a monomer of 130 kDa and a 60 kDa protein, both of which are 2-ME resistant. Cross-immunoblotting studies showed that the anti-dimer antibody recognized the dimer protein as well as the 130 and 60 kDa components. In contrast, the anti-130 kDa antibody gave the strongest signal on blots of reducing gels indicating that the monomer is largely formed by in vitro reduction with 2-ME. All four antibodies recognized membrane antigens on chicken embryo fibroblasts infected with MDV vaccine viruses representative of the three serotypes and in addition, neutralized the homologous MDV isolate. The anti-dimer antibody was greatest, the anti-monomer antibody was the weakest and the anti-60 kDa antibody intermediate in neutralizing efficacy to all four viruses. We conclude from these studies that the B antigen presents at least two classes of neutralizing epitopes: one is discontinuous and of broad specificity on the intact dimer molecule and the other, on the 130 and 60 kDa proteins, is continuous and of lower avidity.  相似文献   
105.
Marek's disease (MD) is a highly contagious lymphoproliferative disease of chickens caused by a herpesvirus, while reticuloendotheliosis (REV) virus is an avian C-type retrpvirus that causes bursal and nonbursal lymphomas which often closely resemble MDV lymphomas. To provide a rapid and sensitive means of diagnosing and differentiating between these two neoplastic conditions, we have applied the PCR. The primers chosen to detect MDV sequences flank the 132 bp tandem repeat of the BamHI-H fragment, whose PCR product is specific for serotype 1 MDVs. The primers selected for REV are based on proviral spleen necrosis virus-long terminal repeat (SNV-LTR) sequences, and can identify both defective and non-defective REVs. The PCR for field isolates of both viruses was standardized with DNA extracted from chick embryo fibroblasts (CEF) infected with various Israeli isolates of MDV and REV. All chickens were examined for REV antibodies by ELISA, REV isolation was performed in CEF and the tumours were examined histopathologically. In some instances, MDV- and REV-PCRs were performed on whole blood DNA and tumour DNA from the same bird. Normal and tumour-bearing birds from a total of 16 chicken and turkey flocks were studied by PCR. These included three laying flocks with MD, two pullet flocks with neurolymphomatosis, four laying flocks that were the progeny of a REV antibody positive flock, four other REV antibody positive flocks, one turkey flock and two chicken flocks with an immunodeficiency syndrome. Some flocks were bled two or three times at 1- to 3-month intervals. We also analysed 30 normal grandparent light breeding birds. Compared to virus isolation, PCR was more sensitive in detecting MDV and REV sequences. It appears, therefore, that PCR is an efficacious and sensitive method for differential diagnosis of tumour-bearing and immunodeficient birds.  相似文献   
106.
Urethane-induced pulmonary adenomas in mice have two distinct histologic growth patterns--solid and papillary. The development of these tumors between 14 and 56 weeks was investigated in A/J mice. Solid tumor multiplicity remained constant from 14 to 56 weeks, whereas papillary and total tumor multiplicities increased in parallel between 14 and 28 weeks and remained constant through 56 weeks. The simplest explanation of these results is that solid and papillary adenomas arise independently, possibly from different cell types. The cell type of origin of these primary mouse lung tumors was investigated histochemically. Succinate dehydrogenase (SDH) histochemistry readily stained bronchiolar epithelial cells, but alveolar epithelial cells exhibited only slight enzymatic activity. Urethane-induced papillary adenomas exhibited intense SDH staining, whereas solid adenomas stained very lightly. Since Clara cells and type II pneumocytes are the only cells capable of proliferation in the bronchiolar and alveolar epithelia, respectively, the relative SDH activities of these adenomas is consistent with a hypothesis that solid tumors arise from type II pneumocytes and papillary tumors arise from Clara cells.  相似文献   
107.
The effect of chemical bursectomy (3-5 mg testosterone cypionate injected at 12 days in ovo followed by 4-0 mg cyclophosphamide intraperitoneally at days 1 and 2 post-hatching) on concentration of immunoglobulins in tears and serum of chickens was investigated. Tears and serum samples were collected from bursectomized and normal control birds between days 26 and 120 post-hatching and were assayed for IgA, 7SIg and IgM concentrations using double gel-diffusion and radial immunodiffusion. No immunoglobulins other than passively acquired 7SIg were detected in the sera or tears of 23 out of 30 bursectomized birds throughout the time period. Sera were also assayed for natural agglutinins; normal birds had titres for rabbit erythrocytes which gradually increased from a mean of 1:24 at day 26 to 1:280 at day 120, while bursectomized chickens had titres of less than 1:8 throughout the experimental period. It was concluded that chemical bursectomy effectively abolished the secretory immunoglobulins normally present in tears as well as serum immunoglobulins.  相似文献   
108.
Activating mutations in Ras oncoproteins represent attractive targets for cancer immunotherapy, but few vectors capable of generating immune responses required for tumor killing without vector neutralization have been described. Whole recombinant yeast heterologously expressing mammalian mutant Ras proteins were used to immunize mice in a carcinogen-induced lung tumor model. Therapeutic immunization with the whole recombinant yeast caused complete regression of established Ras mutation-bearing lung tumors in a dose-dependent, antigen-specific manner. In combination with the genomic sequencing of tumors in patients, the yeast-based immunotherapeutic approach could be applied to treat Ras mutation-bearing human cancers.  相似文献   
109.
Inhibition of cyclooxygenase (COX) activity decreases eicosanoid production and prevents lung cancer in animal models. Prostaglandin (PG) I(2) (PGI(2), prostacyclin) is a PGH(2) metabolite with anti-inflammatory, antiproliferative, and antimetastatic properties. The instability of PGI(2) has limited its evaluation in animal models of cancer. We hypothesized that pulmonary overexpression of prostacyclin synthase may prevent the development of murine lung tumors. Transgenic mice with selective pulmonary prostacyclin synthase overexpression were exposed to two distinct carcinogenesis protocols: an initiation/promotion model and a simple carcinogen model. The transgenic mice exhibited significantly reduced lung tumor multiplicity (tumor number) in proportion to transgene expression, a dose-response effect. Moreover, the highest expressing mice demonstrated reduced tumor incidence. To investigate the mechanism for protection, we evaluated PG levels and inflammatory responses. At the time of sacrifice following one carcinogenesis model, the transgenics exhibited only an increase in 6-keto-PGF(1alpha), not a decrease in PGE(2). Thus, elevated PGI(2) levels and not decreased PGE(2) levels appear to be necessary for the chemopreventive effects. When exposed to a single dose of butylated hydroxytoluene, transgenic mice exhibited a survival advantage; however, reduction in alveolar inflammatory response was not observed. These studies demonstrate that manipulation of PG metabolism downstream from COX produces even more profound lung cancer reduction than COX inhibition alone and could be the basis for new approaches to understanding the pathogenesis and prevention of lung cancer.  相似文献   
110.
Although adenocarcinoma is rapidly becoming the most common form of lung cancer in the United States, the difficulty in obtaining lung cancer families and representative samples of the various stages of adenocarcinoma progression has led to intense study of mouse models. As a powerful approach to delineating molecular changes, we have analyzed 15 early-passage mouse cell lines by spectral karyotyping. Entire copies of chromosomes 1, 2, 6, 12, 15, and 19 were gained, and entire copies of chromosomes 4, 7, 8, and 14 were lost. Significant gains of portions of chromosome 1 (93% of the tumor cell lines analyzed), chromosome 2 (53%), chromosome 6 (73%), chromosome 7 (80%), chromosome 12 (47%), and chromosome 15 (73%) and partial loss of chromosome 4 (87%), chromosome 7 (80%), chromosome 8 (53%), chromosome 10 (33%), and chromosome 14 (33%) were observed. Recurrent translocations included 10:del(10)(A1::C1), t(4;8)(C4;A1), and der (1;12)(C2;C2). The minimal regions of chromosomal alteration, 1G1, 2F1, 4C4, 6D, 7F1, 8B3, and 12C2, contain putative susceptibility genes for mouse lung adenocarcinoma. Chromosomal regions containing susceptibility genes linked to tumor size were frequently amplified, whereas regions with susceptibility loci linked to tumor multiplicity were deleted. Similar linkage groups are altered in human lung adenocarcinoma, implying that the mouse is a valid genetic model for the study of human lung adenocarcinoma susceptibility.  相似文献   
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