全文获取类型
收费全文 | 191篇 |
免费 | 6篇 |
国内免费 | 4篇 |
专业分类
儿科学 | 6篇 |
妇产科学 | 7篇 |
基础医学 | 12篇 |
口腔科学 | 4篇 |
临床医学 | 19篇 |
内科学 | 74篇 |
皮肤病学 | 2篇 |
神经病学 | 2篇 |
特种医学 | 51篇 |
外科学 | 5篇 |
综合类 | 7篇 |
预防医学 | 4篇 |
眼科学 | 1篇 |
药学 | 3篇 |
肿瘤学 | 4篇 |
出版年
2023年 | 1篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2017年 | 1篇 |
2015年 | 3篇 |
2014年 | 3篇 |
2013年 | 1篇 |
2012年 | 4篇 |
2011年 | 3篇 |
2010年 | 5篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 7篇 |
2006年 | 3篇 |
2005年 | 1篇 |
2001年 | 1篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 13篇 |
1996年 | 11篇 |
1995年 | 10篇 |
1994年 | 21篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 9篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 8篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1967年 | 1篇 |
1959年 | 6篇 |
1958年 | 7篇 |
1957年 | 1篇 |
1956年 | 2篇 |
1955年 | 2篇 |
1949年 | 2篇 |
排序方式: 共有201条查询结果,搜索用时 15 毫秒
41.
We have investigated the mechanisms by which colony-stimulating factor (CSF)-inducing biological response modifiers (BRM) may have beneficial effects on tumor-bearing hosts undergoing anti-tumor therapy. First, we have documented that treatment of mice with the chemically defined BRM maleic anhydride divinyl ether copolymer (MVE-2), which induces CSF secretion by macrophages (M phi) and bone marrow cells (BMC), significantly increased growth and differentiation of normal myelopoietic cells and counteracted the myelosuppressive effects of cyclophosphamide (CY). Second, we established that MVE-2 may exert CSF- mediated antitumor effects on certain leukemic tumor cells. Serum from mice pretreated in vivo with MVE-2, which contained CSF, induced terminal differentiation of cloned tumor cells from the CSF responsive WEHI-3B D+ subline in vitro, but not from the WEHI-3B D- subline, which is unresponsive to CSF. In vivo experiments showed that treatment of mice bearing the WEHI-3B D+ tumor first with CY and three days later with the CSF inducer MVE-2, significantly increased their survival time and rendered 20% to 50% of the tumor-bearing mice disease free. No such effects were obtained in mice bearing the WEHI-3B D- tumor. Thus, the induction of CSF or other differentiation factors by some BRMs may result in therapeutic effects against certain leukemias based on at least two distinct mechanisms: In addition to their restorative effects on normal bone marrow functions, CSF-inducing BRMs may also prevent further leukemogenesis by induction of terminal differentiation of leukemic cells. 相似文献
42.
43.
Cryptic structural lesions in refractory partial epilepsy: MR imaging and CT studies 总被引:4,自引:0,他引:4
Ormson MJ; Kispert DB; Sharbrough FW; Houser OW; Earnest F th; Scheithauer BW; Laws ER Jr 《Radiology》1986,160(1):215-219
Results of contrast material-enhanced computed tomography (CT) and T2-weighted spin-echo magnetic resonance (MR) imaging were correlated with pathologic findings in 25 patients treated surgically for refractory partial epilepsy. Of 12 lesions present, ten (83%) were detected by MR imaging and seven (58%) by CT scanning. Of nine low-grade gliomas, eight were detected by MR imaging and four by CT scanning. One posttraumatic scar and one case of temporal lobe atrophy were better demonstrated by MR imaging. A small, thrombosed arteriovenous malformation was the only lesion detected by CT scanning but not by MR imaging. No lesions were detected in 13 patients with mild gliosis and one patient with a 1.2-cm grade 1 astrocytoma. Although more sensitive than CT for detection of structural lesions in patients with refractory partial epilepsy, MR imaging resulted in a 25% false-negative diagnostic rate when a repetition time of 2,000 msec and echo time of 60 msec were used. Multi-echo imaging with at least one long echo time may be needed to increase the sensitivity of MR imaging in these patients. 相似文献
44.
45.
46.
Transforming growth factor beta 1 directly and reversibly inhibits the initial cell divisions of long-term repopulating hematopoietic stem cells 总被引:4,自引:3,他引:4
Hematopoiesis appears to be regulated, in part, by a balance between extracellular positive and negative growth signals. Transforming growth factor beta-1 (TGF-beta 1) has been shown to be a negative regulator of primitive hematopoietic cells. This study examined the direct effect of TGF-beta 1 on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC) in vitro. We previously reported a cell fractionation approach that includes the selection of low Hoescht 33342/low Rhodamine 123 (low Ho/Rh) cell fractions that are highly enriched for long-term repopulating cells (LTR-HSC) and also clone to a very high efficiency in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6: 90% to 100% of individually cultured low Ho/Rh cells formed high proliferative potential clones. This high cloning efficiency of an LTR-HSC enriched cell population enabled proliferation inhibition studies to be more easily interpreted. In this report, we show that the continuous presence of TGF-beta 1 directly inhibits the cell division of essentially all low Ho/Rh cells (in a dose-dependent manner) during their 0 to 5th cell division in vitro. Therefore, it follows that TGF-beta 1 must directly inhibit the proliferation of LTR-HSC contained within these low Ho/Rh cells. The time required for some low Ho/Rh cells to undergo their first cell division in vitro was also prolonged in the presence of TGF-beta 1. Furthermore, when low Ho/Rh cells were exposed to TFG-beta 1 for varying lengths of time before neutralization of the TGF-beta 1 by monoclonal antibody, the ability to form macroclones was markedly decreased after approximately 4 days of TGF-beta 1 exposure. In addition, 1 to 10 ng/mL of TGF-beta 1 resulted in a maintenance of high proliferative potential-colony-forming cell (HPP-CFC) during 8 days of culture compared with loss of HPP-CFC in cultures with no added TGF- beta 1. In conclusion, this study shows that TGF-beta 1 directly inhibits the initial stages of proliferation of LTR-HSC and appears to slow the differentiation of daughter cells of low Ho/Rh cells. 相似文献
47.
Preijers FW; De Witte T; Wessels JM; De Gast GC; Van Leeuwen E; Capel PJ; Haanen C 《Blood》1989,74(3):1152-1158
Seven patients with high-risk acute T-cell lymphoblastic leukemia (T- ALL) and six with T cell lymphoma (T-LL) were treated with autologous bone marrow transplantation (ABMT) after in vitro purging of their bone marrow with WT1 (CD7)-ricin A-chain immunotoxin. CD7 expression on the tumor cells showed large variations between the individual patients and was highly related to the specific cytotoxicity of WT1-ricin A. Incubation of bone marrow with up to 10(-8)mol/L WT1-ricin A in the presence of 6 mmol/L NH4Cl did not compromise the growth potential of the hematopoietic progenitors CFU-GM, CFU-GEMM, and BFU-E. Hematologic engraftment (greater than 10(9) leukocytes/L) occurred within a normal time period (median, 17 days). Seven patients are alive and in complete remission (CR) at 48+, 44+, 40+, 26+, 11+, 7+, and 6+ months after ABMT. Four patients relapsed within 6 months after ABMT. Two of them had the lowest CD7 expression on their tumor cells, the other two were transplanted in CR2 and CR3. Two patients died from transplantation related infections. The immunologic reconstitution was delayed, although the numbers of T cells reached normal levels within 1 month. The number of CD7+ cells remained low up to 1 year after transplantation. The T4/T8-ratio was decreased for at least 6 months. The T-cell response to mitogens recovered to normal levels after 1 year. This study shows that ABMT with WT1-ricin A purged bone marrow in high-risk T-cell malignancies results in a complete hematopoietic and a delayed immunologic reconstitution. The actuarial relapse free survival is 61% at 3 years. 相似文献
48.
The initial establishment of hamster long-term bone marrow (LTBM) cultures requires formation of an adherent stromal layer, but continued long-term proliferation of these cultures is best accomplished by removal of the suspension cells from the adherent layer and subsequent incubation in liquid suspension culture. Continued maintenance of bone marrow cells in the presence of the adherent layer for more than four to six weeks leads to a decline and eventual disappearance of erythroid and multipotent colony-forming cells. Addition of erythropoietin to LTBM suspension cultures produces mature, hemoglobinized erythrocytes. Incubation of the same cells plus erythropoietin in the presence of autologous parental adherent layers markedly inhibits both terminal erythroid differentiation and the number of detectable erythroid burst- forming units (BFU-Es). This erythroid inhibition occurs primarily within the first 24 hours with little or no effect on CFU-GEMMs or granulocyte-macrophage colony-forming units (GM-CFUs). However, continued incubation for seven days produces a reduction in all parameters. Removal of suspension cells from the adherent layer and restimulation with erythropoietin allows regeneration of erythropoiesis. Pretreatment of suspension cells with erythropoietin for 96 hours before exposure to the adherent culture only slightly inhibits erythropoiesis, suggesting that more mature erythroid progenitors are unaffected. Conditioned medium from the marrow adherent layer (ALCM) produces similar erythroid inhibitory effects in LTBM cultures with as little as two hours of incubation. The inhibition is actively produced by the adherent cells, since cycloheximide abolishes its production, while indomethacin has no apparent effect. Adherent marrow stromal cells may regulate hemopoiesis through negative as well as positive humoral signals, and they are particularly effective in erythroid regulation. 相似文献
49.
Transforming growth factor beta selectively inhibits normal and leukemic human bone marrow cell growth in vitro 总被引:12,自引:1,他引:12
The effects of transforming growth factor beta 1 or beta 2 (TGF-beta 1 or -beta 2) on the in vitro proliferation and differentiation of normal and malignant human hematopoietic cells were studied. Both forms of TGF- beta suppressed both the normal cellular proliferation and colony formation induced by recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the presence of GM-CSF or IL-3, optimal concentrations of TGF-beta (400 pmol/L) inhibited colony formation by erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor cells by 90% to 100%, whereas granulocyte or monocyte cluster formation was not inhibited. In contrast, neither form of TGF-beta had any effect on G- CSF-induced hematopoiesis. The suppressive action appeared to be mediated directly by TGF-beta since antiproliferative responses were also observed in accessory cell-depleted bone marrow cells. In contrast to normal bone marrow cells, both GM- and G-CSF-induced proliferation of cells from patients with chronic myelogenous leukemia were suppressed in a dose-dependent manner by TGF-beta. Differential effects of TGF-beta on the proliferation of established leukemic lines were also observed since most cell lines of myelomonocytic nature studied were strongly inhibited where erythroid cell lines were either insensitive or poorly inhibited by TGF-beta. These results suggest that TGF-beta is an important modulator of human hematopoiesis that selectively regulates the growth of less mature hematopoietic cell populations with a high proliferative capacity as opposed to more differentiated cells, which are not affected by TGF-beta. 相似文献
50.
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