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排序方式: 共有159条查询结果,搜索用时 15 毫秒
41.
Downregulation of proinflammatory cytokine release in whole blood from septic patients 总被引:20,自引:2,他引:20
Ertel W; Kremer JP; Kenney J; Steckholzer U; Jarrar D; Trentz O; Schildberg FW 《Blood》1995,85(5):1341-1347
Using animal models or healthy volunteers, injection of lipopolysaccharide (LPS) or bacteria causes activation of macrophages with excessive synthesis and secretion of proinflammatory cytokines. Although these models mimic the effects of LPS in the host, they may represent more of an experimental expression of endotoxemia than natural infection itself. Therefore, as an ex vivo model of sepsis, whole blood from 15 patients with severe sepsis and 20 control patients without infection was stimulated with LPS to study the kinetics of mRNA expression and release of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6. Stimulation of whole blood with 1 microgram/mL LPS resulted in a maximum increase of cytokine secretion in the control group, while a marked (P < .01) depression of TNF-alpha, IL-1 beta, and IL-6 release was observed in the septic group, which persisted up to 10 days after study enrollment. While IL-1 beta mRNA expression was similar in peripheral blood mononuclear cells (PBMCs) harvested from LPS-stimulated whole blood in septic and control patients, the half-life and consequently the expression of TNF-alpha and IL-6 mRNA were strongly reduced in the septic group. These data indicate a downregulatory mechanism of cytokine release in whole blood from patients with severe sepsis that occurs on different levels. Although excessive secretion of proinflammatory cytokines has been considered deleterious for the host, the reduced capacity of PBMCs in whole blood from septic patients to synthesize and secrete proinflammatory cytokines to an inflammatory stimulus may result in immunodeficiency, because these cytokines in low concentrations are involved in the upregulation of essential cellular and humoral immune functions. 相似文献
42.
Rusten LS; Jacobsen FW; Lesslauer W; Loetscher H; Smeland EB; Jacobsen SE 《Blood》1994,83(11):3152-3159
Tumor necrosis factor alpha (TNF alpha) has previously been reported to have both inhibitory and stimulatory effects on hematopoietic progenitor cells. Specifically, TNF alpha has been proposed to stimulate early hematopoiesis in humans. In the present study we show that TNF alpha, in a dose-dependent fashion, can potently inhibit the growth of primitive high proliferative potential colony-forming cells (HPP-CFCs) stimulated by multiple cytokine combinations. Using agonistic antibodies to the p55 and p75 TNF receptors or TNF alpha mutants specific for either of the two TNF receptors, we show that both receptors can mediate this inhibition. In contrast, the potent stimulation of interleukin-3 (IL-3) plus granulocyte-macrophage colony- stimulating factor (GM-CSF) induced HPP-CFC colony formation observed at low concentrations of TNF alpha (2 ng/mL) was only a p55-mediated event. Moreover, the stimulatory effects of TNF alpha on GM-CSF or IL-3- induced colony formation, as well as the inhibition of G-CSF-induced colony growth, were also exclusively signaled through the p55 TNF receptor. Taken together, our results suggest that the inhibitory effects of TNF alpha on primitive bone marrow progenitor cells are mediated through both p55 and p75 TNF receptors, whereas the p55 receptor exclusively mediates the bidirectional effects on more mature, single factor-responsive bone marrow progenitor cells as well as stimulation of IL-3 plus GM-CSF-induced HPP-CFC colony growth. 相似文献
43.
Bluman EM; Schnier GS; Avalos BR; Strout MP; Sultan H; Jacobson FW; Williams DE; Carson WE; Caligiuri MA 《Blood》1996,88(10):3887-3893
44.
Human umbilical vein endothelial cells display high-affinity c-kit receptors and produce a soluble form of the c-kit receptor 总被引:4,自引:3,他引:4
Stem cell factor (SCF) is a hematopoietic growth factor produced by fibroblasts and endothelial cells that stimulates the growth of primitive hematopoietic cells. SCF triggers cell growth by binding to the c-kit receptor. Because endothelial cells can respond to certain hematopoietic growth factors, we tested human umbilical vein endothelial cells for display of the c-kit receptor and examined the effect of SCF on endothelial cell proliferation, adhesion molecule expression, and production of tissue factor. Quantitative binding experiments with 125I-SCF showed both high-affinity (Kd = 42 pmol/L) and low-affinity (Kd = 1.7 nmol/L) c-kit receptors. There were approximately 1,100 high-affinity c-kit receptors, and 5,400 low- affinity c-kit receptors per endothelial cell. Enzyme immunoassays showed that endothelial cells released soluble c-kit receptor and SCF. The transmembrane form of SCF was detected by indirect immunofluorescence analysis using monoclonal or polyclonal anti-SCF receptor antibodies. The addition of SCF (100 ng/mL) did not alter endothelial cell proliferation over a 7-day period. Similarly, there was no change in the release of tissue factor or expression of inducible endothelial adhesion molecules (intercellular adhesion molecule-1, endothelial-leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1) measured by enzyme-linked immunosorbant assay at 4 and 24 hours after SCF addition. The neutralizing anti-c-kit receptor monoclonal antibody SR-1 blocked binding of 125I-SCF to the c- kit receptor by 98% but did not alter endothelial cell proliferation or adhesion-molecule expression. c-kit receptors were also detected on adult endothelial cells lining small blood vessels in normal human lymph nodes. These data indicate that normal human endothelial cells produce SCF and show high-affinity c-kit receptors that have the capacity to dimerize. The lack of response to exogenous SCF may be because of intracellular activation of the c-kit receptor via autocrine production of SCF. Alternatively, SCF and c-kit may play a role other than stimulation of proliferation, adhesion-molecule display, or tissue factor production by endothelial cells. The production of soluble c-kit receptors by normal human endothelial cells may serve to regulate the bioactivity of SCF within the bone marrow microenvironment. 相似文献
45.
46.
Grzegorzewski KJ; Komschlies KL; Franco JL; Ruscetti FW; Keller JR; Wiltrout RH 《Blood》1996,88(11):4139-4148
Administration of recombinant human interleukin-7 (rhIL-7) to mice increases the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU- GEMM]) from the bone marrow (BM) to peripheral organs, including blood, and also increases the number of primitive progenitor and stem cells in the peripheral blood (PB). We now report that combined treatment of mice with rhIL-7 and recombinant human granulocyte-colony stimulating factor (rhG-CSF) stimulates a twofold to 10-fold increase in the total number of PB CFU-c, and a twofold to fivefold increase in the total number of PB CFU-spleen at day 8 (CFU-S8) over the increase stimulated by rhIL-7 or rhG-CSF alone. In addition, the quality of mobilized cells with trilineage, long-term marrow-repopulating activity is maintained or increased in mice treated with rhIL-7 and rhG-CSF compared with rhIL- 7 or rhG-CSF alone. These differences in mobilizing efficiency suggest qualitative differences in the mechanisms by which rhIL-7 and rhG-CSF mobilize progenitor cells, in fact, the functional status of progenitor cells mobilized by rhIL-7 differs from that of cells mobilized by rhG- CSF in that the incidence of actively cycling (S-phase) progenitors obtained from the PB is about 20-fold higher for rhIL-7-treated mice than for mice treated with rhG-CSF. These results suggest the use of rhIL-7-mobilized progenitor/stem cells for gene-modification and tracking studies, and highlight different functions and rates of repopulation after reconstitution with PB leukocytes obtained from mice treated with rhIL-7 versus rhG-CSF. 相似文献
47.
48.
Neuer A; Lam KN; Tiller FW; Kiesel L; Witkin SS 《Human reproduction (Oxford, England)》1997,12(5):925-929
Recent evidence suggests that Chlamydia trachomatis can persist in the
female upper genital tract in an unculturable state. Since unsuspected C.
trachomatis infection has been associated with adverse in-vitro
fertilization (IVF) outcome we sought to detect further evidence of C.
trachomatis in the genital tracts of women undergoing IVF. The prevalence
and distribution of antibodies to the major structural proteins of C.
trachomatis in paired follicular fluid and sera of women undergoing IVF
were examined. Sera and follicular fluid samples from 149 women were
assayed for immunoglobulin (Ig)G and IgA antibodies to two C. trachomatis
antigens, the major outer membrane protein (MOMP) and a recombinant
lipopolysaccharide (rLPS) fragment. Additionally, the expression of human
60 kDa heat shock protein (hsp 60) in follicular fluid was determined. All
cervical and follicular fluid samples were negative for C. trachomatis by
polymerase chain reaction, ligase chain reaction and DNA probe. Sera from
60% of the subjects were positive for antichlamydial rLPS IgG; 36% were
positive for anti-MOMP IgG. Similarly, rLPS-directed and MOMP-directed IgA
were detected in sera of 34 and 14% of the subjects respectively. IgG
antibodies to MOMP and rLPS were detected in 42 and 41% of the follicular
fluid examined respectively. Anti-MOMP IgA was identified in 8.7% of the
follicular fluid while 27.5% were positive for anti-rLPS IgA. Human hsp 60
expression was documented in 11.6% of the follicular fluid tested. IgA
antibodies to both MOMP (P = 0.03) and rLPS (P = 0.02) in follicular fluid
were associated with a failure to become pregnant after embryo transfer.
IgG antibodies in sera and follicular fluid and IgA antibodies in sera were
unrelated to IVF outcome. Similarly only anti- MOMP IgA (P = 0.02) and
anti-rLPS IgA (P = 0.04) in follicular fluid were correlated with human hsp
60 expression in follicular fluid. The unique association between IgA
antibodies to two chlamydial antigens in follicular fluid and both hsp 60
expression and IVF failure provides further support for the possibility
that a persistent upper genital tract chlamydial infection contributes to
IVF failure in some women.
相似文献
49.
Cyclic adenosine monophosphate response to prostaglandin E2 on subpopulations of human lymphocytes 下载免费PDF全文
M Kasai JC Leclerc L McVay-Boudreau FW Shen H Cantor 《The Journal of experimental medicine》1979,150(5):1260-1264
Receptors for prostaglandin E2 or histamine were measured on subpopulations of human lymphocytes, using the cyclic AMP increase after exposure to prostaglandin or histamine as an indicator for the presence of receptors. The cyclic AMP response to prostaglandin E2 was similar in unfractionated lymphocytes and the T-enriched and T-depleted fractions. Within the T-enriched population, T cells bearing a receptor for the Fc portion of IgG (T gamma-cells) had a 27.4-fold rise in cyclic AMP after exposure to prostaglandin E2, whereas the remaining T cells (non-T gamma cells) had a fourfold increase. It would appear that prostaglandin receptors are concentrated on a small subfraction of T gamma cells, comprising approximately 15% of the T-cell population. The cyclic AMP response to histamine was less than twofold in all lymphocyte fractions. 相似文献
50.