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91.
Role of ADP-ribosyl transferase in differentiation of human granulocyte- macrophage progenitors to the macrophage lineage 总被引:6,自引:0,他引:6
Nuclear adenosine diphosphate-ribosyl (ADP-ribosyl) transferase is a chromatin-bound enzyme catalyzing the transfer of ADP-ribose from NAD+ to chromatin proteins. The physiologic function of this covalent modification of chromatin has not been fully established, but roles in both DNA repair and in differentiation have been proposed. We demonstrate that three specific inhibitors of ADP-ribosyl transferase (5-methylnicotinamide, 3-methoxybenzamide, 3-aminobenzamide) inhibit differentiation of human granulocyte-macrophage progenitor cells to the macrophage lineage. Differentiation to the neutrophil-granulocyte lineage is much less affected. The inhibition of macrophage differentiation seems to relate to the ability of these compounds to inhibit ADP-ribosyl transferase. A structural analogue (3- methoxybenzoic acid), which is not inhibitory for the enzyme, did not inhibit macrophage differentiation. Additional evidence for a role of ADP-ribosyl transferase in the differentiation of granulocyte- macrophage progenitors was obtained from experiments in which enzyme activity levels were measured in permeabilized marrow cells. Marrow cell ADP-ribosyl transferase activity increased after 3-hr stimulation by the differentiation/proliferation stimulus--granulocyte-macrophage colony-stimulating activity (GM-CSA). Unstimulated marrow cells showed low or undetectable levels of enzyme activity. 相似文献
92.
Estrogen-induced microsatellite DNA alterations are associated with Syrian hamster kidney tumorigenesis 总被引:4,自引:0,他引:4
Exposure to estrogens is associated with an increase in cancers, including
malignancies of the breast and uterus in humans, and of the kidney in
hamsters. DNA damage induced by metabolic activation of estrogen has been
postulated to result in gene mutations critical for the development of
estrogen-induced kidney tumors in hamsters. As part of our examination of
the genetic consequences of estrogen-induced DNA damage, we searched for
estrogen-induced alterations in microsatellite DNA, a frequent site of
mutation in tumors. Genomic DNA isolated from kidney of hamsters treated
with estradiol, from estrogen-induced kidney tumors and from untreated
age-matched controls, was examined by Southern blot analysis with three
multi-locus oligonucleotide probes: (GACA)4, (CAC)6 and (CAG)6. Alterations
in DNA fragments containing GACA and CAC tandem repeats were detected in
kidney DNA of hamsters treated with hormone for 3 and 4 months, whereas no
such effects were seen in control animals. In estrogen-induced tumors,
microsatellite alterations were observed in fragments that contain these
same two repeat sequences and also CAG repeat sequences. The induction of
microsatellite alterations by estradiol in kidney DNA preceding
estrogen-induced renal malignancy may play a role in hormone-induced
tumorigenesis.
相似文献
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CZ Zhu JP Mikusa Y Fan PR Hollingsworth M Pai P Chandran AV Daza BB Yao MJ Dart MD Meyer MW Decker GC Hsieh P Honore 《British journal of pharmacology》2009,157(4):645-655
Background and purpose:
Activation of cannabinoid (CB) receptors decreases nociceptive transmission in inflammatory or neuropathic pain states. However, the effects of CB receptor agonists in post-operative pain remain to be investigated. Here, we characterized the anti-allodynic effects of WIN 55,212-2 (WIN) in a rat model of post-operative pain.Experimental approach:
WIN 55,212-2 was characterized in radioligand binding and in vitro functional assays at rat and human CB1 and CB2 receptors. Analgesic activity and site(s) of action of WIN were assessed in the skin incision-induced post-operative pain model in rats; receptor specificity was investigated using selective CB1 and CB2 receptor antagonists.Key results:
WIN 55,212-2 exhibited non-selective affinity and agonist efficacy at human and rat CB1 versus CB2 receptors. Systemic administration of WIN decreased injury-induced mechanical allodynia and these effects were reversed by pretreatment with a CB1 receptor antagonist, but not with a CB2 receptor antagonist, given by systemic, intrathecal and supraspinal routes. In addition, peripheral administration of both CB1 and CB2 antagonists blocked systemic WIN-induced analgesic activity.Conclusions and implications:
Both CB1 and CB2 receptors were involved in the peripheral anti-allodynic effect of systemic WIN in a pre-clinical model of post-operative pain. In contrast, the centrally mediated anti-allodynic activity of systemic WIN is mostly due to the activation of CB1 but not CB2 receptors at both the spinal cord and brain levels. However, the increased potency of WIN following i.c.v. administration suggests that its main site of action is at CB1 receptors in the brain.British Journal of Pharmacology (2009) 157, 645–655; doi:10.1111/j.1476-5381.2009.00184.x; published online 3 April 2009 相似文献96.
MS Chaya AV Kurpad HR Nagendra R Nagarathna 《BMC complementary and alternative medicine》2006,6(1):28-6
Background
Different procedures practiced in yoga have stimulatory or inhibitory effects on the basal metabolic rate when studied acutely. In daily life however, these procedures are usually practiced in combination. The purpose of the present study was to investigate the net change in the basal metabolic rate (BMR) of individuals actively engaging in a combination of yoga practices (asana or yogic postures, meditation and pranayama or breathing exercises) for a minimum period of six months, at a residential yoga education and research center at Bangalore. 相似文献97.
98.
Moses AV; Williams S; Heneveld ML; Strussenberg J; Rarick M; Loveless M; Bagby G; Nelson JA 《Blood》1996,87(3):919-925
The majority of human immunodeficiency virus (HIV)-seropositive patients develop bone marrow abnormalities associated with hematopoietic malfunction during the progression of disease. One important manifestation of HIV-associated hematopoietic dysfunction is that after myelosuppression, bone marrow recovery, a process known to be mediated in part by the production of stromal cell-derived hematopoietic growth factors, is impaired. We sought to test the hypothesis that bone marrow stromal cells are infected by HIV-1 in vivo and that production of certain stromal cell-derived hematopoietic growth factors is deficient as a consequence. In this report, we demonstrate that bone marrow microvascular endothelial cells (MVEC), a key element of the stroma, are the predominant cells infected by HIV (5% to 20%) in bone marrow stromal cultures obtained from 11 consecutive HIV-seropositive patients. Although HIV-infected stromal cultures enriched for MVEC constitutively express normal levels of interleukin (IL)-4, IL-6, granulocyte (G)-colony-stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, tumor necrosis factor (TNF)- alpha, transforming growth factor (TGF)-beta, and Steel factor, IL-1 alpha-induced release of IL-6 and G-CSF is significantly reduced in these cultures. These observations suggest that HIV infection of bone marrow MVEC reduces the capacity of hematopoietic stroma to respond to regulatory signals that normally augment blood cell production during periods of increased demand. 相似文献
99.
Heslop HE; Gottlieb DJ; Bianchi AC; Meager A; Prentice HG; Mehta AB; Hoffbrand AV; Brenner MK 《Blood》1989,74(4):1374-1380
Interleukin-2 (IL-2) therapy may improve immune reconstitution and reduce the risk of leukemic relapse in the setting of minimal residual disease by augmenting cytotoxic effector mechanisms directed at residual malignant cells. In addition, IL-2 in vitro promotes the release of cytokines including gamma-interferon (gamma-IFN) and tumor necrosis factor (TNF), which also possess antileukemic activity and can enhance granulocyte function. To determine if IL-2 infusion induces release of gamma-IFN and TNF in vivo in sufficient quantity to mediate these effects, we have measured serum levels of these cytokines and secretion by lymphocytes obtained from patients receiving this cytokine in a phase 1 trial. Serum gamma-IFN was undetectable pre-IL-2 and increased to 1.5 to 17 U/mL during IL-2 infusion (P less than .05). Culture of patient lymphocytes for 48 hours produced 1.2 U gamma-IFN/2 x 10(6) cells/mL pre-IL-2 rising to 50 U/2 x 10(6) cells/mL when the lymphocytes were obtained during therapy (P less than .05). Lymphocyte subset analysis showed that both CD3+ and CD16+ cells secreted gamma- IFN in response to IL-2. TNF secretion by lymphocytes also rose during IL-2 infusion from a mean of 5 U/mL to 14.4 U/mL (P less than .01) although no rise was seen in serum levels. The material secreted by IL- 2-stimulated lymphocytes is bioactive as addition of supernatants from lymphocytes obtained during IL-2 therapy to cultures of myeloid blasts significantly inhibited clonogenic growth. IL-2-induced secretion of these cytokines mediated this inhibition as it could be partially blocked by either anti-gamma-IFN or anti-TNF antibodies. Preincubation of granulocytes with the same supernatants produced enhanced oxidative metabolism, measured by chemiluminescence in response to N-formyl- methionyl-leucyl-phenylalanine (FMLP). This effect also could be partially abrogated by anti-gamma-IFN and anti-TNF antibodies. Therefore, secondary cytokine secretion may boost granulocyte function and contribute to the antileukemic effects of IL-2 infusion in patients following bone marrow transplantation or chemotherapy. 相似文献
100.