全文获取类型
收费全文 | 694篇 |
免费 | 41篇 |
国内免费 | 46篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 52篇 |
妇产科学 | 21篇 |
基础医学 | 92篇 |
口腔科学 | 38篇 |
临床医学 | 95篇 |
内科学 | 177篇 |
皮肤病学 | 10篇 |
神经病学 | 26篇 |
特种医学 | 117篇 |
外科学 | 29篇 |
综合类 | 10篇 |
预防医学 | 22篇 |
眼科学 | 3篇 |
药学 | 54篇 |
1篇 | |
肿瘤学 | 32篇 |
出版年
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 5篇 |
2019年 | 5篇 |
2018年 | 10篇 |
2017年 | 11篇 |
2016年 | 16篇 |
2015年 | 15篇 |
2014年 | 21篇 |
2013年 | 26篇 |
2012年 | 13篇 |
2011年 | 15篇 |
2010年 | 20篇 |
2009年 | 22篇 |
2008年 | 12篇 |
2007年 | 43篇 |
2006年 | 25篇 |
2005年 | 13篇 |
2004年 | 7篇 |
2003年 | 9篇 |
2002年 | 18篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 11篇 |
1998年 | 44篇 |
1997年 | 53篇 |
1996年 | 54篇 |
1995年 | 46篇 |
1994年 | 30篇 |
1993年 | 30篇 |
1992年 | 2篇 |
1991年 | 12篇 |
1990年 | 7篇 |
1989年 | 15篇 |
1988年 | 24篇 |
1987年 | 19篇 |
1986年 | 14篇 |
1985年 | 15篇 |
1984年 | 6篇 |
1983年 | 10篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 11篇 |
1978年 | 4篇 |
1977年 | 8篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1973年 | 2篇 |
1967年 | 2篇 |
1960年 | 1篇 |
排序方式: 共有781条查询结果,搜索用时 0 毫秒
771.
自身免疫性肝炎患者自身抗体的测定及意义 总被引:2,自引:1,他引:2
目的:探讨自身抗体测定对诊断自身免疫性肝炎的临床意义.方法:采用间接免疫荧光法(IIF)检测47例自身免疫性肝炎患者、158例非自身免疫性肝炎患者及40例健康体检者体内抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗中性粒细胞胞质抗体(ANCA)、抗线粒体抗体(AMA)等自身抗体,ELISA法检测抗MPO抗体,并对结果进行回顾性分析.结果:ANA、SMA及ANCA检出率的比较,结果显示AIH中阳性率最高为SMA(66.0%, 31/47),而非AIH中则为6.3%(10/158),两组差异有非常显著性意义(P<0.01).经X2检验, SMA、AMA和MPO抗体检测在AIH与PBC中,均有非常显著性意义(P<0.01).AIH各型自身抗体检测结果表明,AIH-Ⅰ与ANA、SMA和ANCA相关,AIH-Ⅱ与LKM相关,而AIH=Ⅲ与SLA和ANCA相关.结论:血清自身抗体的检测对诊断、治疗和阻止自身免疫性肝炎的发展有着十分重要作用,对提高AIH在临床上同其他肝病鉴别诊断和治疗有着非常重要的意义. 相似文献
772.
Localization of the G-CSF gene on chromosome 17 proximal to the breakpoint in the t(15;17) in acute promyelocytic leukemia 总被引:3,自引:0,他引:3
Simmers RN; Webber LM; Shannon MF; Garson OM; Wong G; Vadas MA; Sutherland GR 《Blood》1987,70(1):330-332
The human granulocyte-colony stimulating factor gene (G-CSF) is localized at 17q11.2-q21, the region of one of the breakpoints in the 15;17 chromosome translocation specific for acute promyelocytic leukemia (APL). As G-CSF induces differentiation and loss of tumorigenicity in myeloid leukemic cells or cell lines, it was possible that the translocation in APL involved the DNA of the G-CSF coding region or its regulatory region. In situ hybridization to chromosomes with the t(15;17) from patients with the APL translocation using a G- CSF cDNA clone revealed that the coding region of this gene is proximal to the t(15;17) breakpoint on chromosome 17. Southern analysis of DNA from patients with the APL translocation showed no differences in hybridization between normal and leukemic cells. These results indicate that the G-CSF coding sequence is not disrupted by the chromosomal rearrangement characteristic of APL. 相似文献
773.
Wang LM; Michieli P; Lie WR; Liu F; Lee CC; Minty A; Sun XJ; Levine A; White MF; Pierce JH 《Blood》1995,86(11):4218-4227
Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3- dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin- like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL- 13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4R alpha) and lack expression of the IL-2 receptor gamma subunit (IL-2R gamma), resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. These results indicate that IL-13 does not use the IL-2R gamma subunit in its receptor complex and that expression of IL-2R gamma enhances, but is not absolutely required for mediating IL-4-induced tyrosine phosphorylation of IRS-1/4PS. 相似文献
774.
Circulating monoclonal B cells expressing P glycoprotein may be a reservoir of multidrug-resistant disease in multiple myeloma 总被引:5,自引:1,他引:5
Multiple myeloma is basically an incurable cancer. Most patients respond initially to chemotherapy with reduction in bone marrow (BM) plasma cells and monoclonal Ig levels, but the disease nearly always recurs and becomes refractory to therapy. The objective of this study was to characterize the expression of the multidrug transport pump, P- glycoprotein 170 (P-gp), in myeloma. The great majority of B cells from peripheral blood mononuclear cells (PBMCs) in myeloma express P-gp, detected by the monoclonal antibody MRK-16. P-gp+ blood B cells exhibit extensive DNA hyperdiploidy, suggesting replicative abnormality characteristic of malignant growth. We speculate these represent a stem cell population in myeloma. The proportion of B cells expressing P-gp was comparable among untreated myeloma patients and those treated with chemotherapy, biologic response modifiers, or off treatment. Among BM cells, P-gp was absent or low in untreated myeloma patients but was expressed at high levels on BM cells from patients previously treated with chemotherapy. For untreated patients the majority of B/plasma cells expressing P-gp are located in PBMCs, not the BM cells. Flow cytometric analysis of rhodamine 123 dye efflux indicated a functional P-gp that was efficiently blocked by verapamil or cyclosporin A (CsA). Both the CD11bhi CD19+ B cells and the T cells in myeloma PBMCs had active CsA-inhibited dye efflux, but monocytes lacked the ability to efflux dye. Nearly all CD38hi plasma cells from myeloma BM cells retained dye, indicating their lack of a functional transport pump. Thus, PBMC B cells may be the predominant set of drug-resistant tumor cells. Myeloma PBMC B cells were cultured with Adriamycin with or without CsA and drug toxicity evaluated by the induction of apoptosis, using flow cytometry to quantitate DNA disruption. No apoptosis was detectable at 0.01 microgram/mL adriamycin, the in vivo steady-state level, with or without CsA. With 0.1 microgram adriamycin, no apoptosis was detectable in the absence of CsA, but with CsA, 66% of B cells initiated DNA disruption, whereas most T cells were spared. This work suggests that currently used drug dosages are too low to effect P-gp+ B- cell death, even in the presence of CsA. We suggest that blood B cells comprise a highly drug-resistant subset of the myeloma B lineage that escapes conventional chemotherapy and may underlie the almost uniform fatal relapse in myeloma patients. 相似文献
775.
Provan D; Bartlett-Pandite L; Zwicky C; Neuberg D; Maddocks A; Corradini P; Soiffer R; Ritz J; Nadler LM; Gribben JG 《Blood》1996,88(6):2228-2235
In chronic lymphocytic leukemia (CLL), clonal rearrangement of the immunoglobulin heavy chain locus (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. At the time of initial presentation, DNA from patients with CLL was polymerase chain reaction (PCR)-amplified using consensus Variable (VH) and Joining (JH) region primers using complementarity determining region III consensus region primers or a panel of VH family-specific framework region 1 (FR1) primers. The clonal product was directly sequenced and patient-specific probes constructed using N region nucleotide sequences. We amplified and sequenced the CDRIII region and designed patient specific oligonucleotide probes for the detection of MRD in 55 of 66 patients (84%, 90% Confidence Intervals (CI): 74% to 90%) with poor prognosis CLL referred for autologous and allogeneic bone marrow transplantation (BMT). To determine the clinical utility of this technique, PCR amplification was performed on patient samples at the time of and following autologous (21 patients) and allogeneic (10 patients) BMT in whom serial bone marrow samples obtained after BMT were available for analysis. We show that the persistence of MRD after BMT is associated with increased probability of relapse. In all cases that have relapsed to date, the IgH CDRII region was identical at the time of initial presentation and at relapse suggesting that clonal evolution of the IgH locus is unusual in this disease. The finding that a significant number of patients remain disease free and with no evidence of PCR-detectable MRD after BMT suggests that high-dose therapy may contribute to improved outcome in selected patients with CLL. 相似文献
776.
Inhibition of delayed-type contact hypersensitivity in mice deficient in both E-selectin and P-selectin 总被引:11,自引:1,他引:11
Leukocyte rolling and emigration in response to inflammatory stimuli appears to involve both E-selectin- and P-selectin-dependent adhesion, which suggests that these molecules have overlapping functions. To clarify their relative contributions in chronic inflammation, we examined delayed-type contact hypersensitivity (DTH) responses in P- selectin, E-selectin, and E-/P-selectin-deficient mice. Oxazolone- induced increases in ear thickness and ear weight were equivalent in wild-type mice and in P-selectin and E-selectin mutants, but were significantly reduced in E-/P-selectin mutants. The number and area of microabscesses on the ears of E-/P-deficient mice were decreased by 72% and 93%, and the number of leukocytes invading the subdermal ear tissue was reduced. T cells from E-/P-deficient mice transferred oxazolone reactivity into naive wild-type mice. However, when donor T cells from wild-type mice were transferred into E-/P-selectin-deficient mice, the DTH response was significantly impaired. These results show that leukocyte recruitment into a subacute inflammatory reaction can occur when either P-selectin or E-selectin is present, but is significantly reduced when both selectins are absent. Both P- and E-selectin are likely to play important roles in the development and maintenance of inflammatory diseases. 相似文献
777.
Fanconi anemia genes act to suppress a cross-linker-inducible p53- independent apoptosis pathway in lymphoblastoid cell lines 总被引:5,自引:1,他引:5
Hypersensitivity to cross-linking agents such as mitomycin C (MMC) is characteristic of cells from patients suffering from the inherited bone marrow failure syndrome. Fanconi anemia (FA). Here, we link MMC hypersensitivity of Epstein-Barr virus (EBV)-immortalized FA lymphoblasts to a high susceptibility for apoptosis and p53 activation. In MMC-treated FA cells belonging to complementation group C (FA-C), apoptosis followed cell cycle arrest in the G2 phase. In stably transfected FA-C cells, plasmid-driven expression of the wild-type cytoplasmic FAC protein relieved MMC-dependent G2 arrest and suppressed p53 activation. However, in both FA and non-FA lymphoblasts, p53 seemed not to be instrumental in the induction of MMC-dependent apoptosis, since overexpression of a dominant-negative p53 mutant failed to affect cell survival. In addition, no differences in the level of Bcl-2 expression, an inhibitor of apoptosis, were detected between FA and non- FA cells either in the absence or presence of MMC. Our findings suggest that FAC and the other putative FA gene products may function in a yet to be identified p53-independent apoptosis pathway. 相似文献
778.
Abnormal assembly of membrane proteins in erythroid progenitors of patients with beta-thalassemia major 总被引:1,自引:1,他引:1
Aljurf M; Ma L; Angelucci E; Lucarelli G; Snyder LM; Kiefer CR; Yuan J; Schrier SL 《Blood》1996,87(5):2049-2056
The life threatening anemia in beta-thalassemia major (Cooley's anemia) is characterized by profound intramedullary lysis, the cause of which is incompletely understood. Using marrow obtained from beta thalassemia major patients undergoing allogeneic bone marrow transplantation in Pesaro Italy, it became possible to directly study the mechanism of the intramedullary hemolysis. Based on our previous studies, we hypothesized that the unmatched alpha globin chains would interfere with normal assembly of erythroid precursor membrane proteins. Patient and control erythroid precursors were reacted with monospecific polyclonal rabbit antibodies directed against spectrin, band 3, and band 4.1 and with a monoclonal anti-alpha globin chain antibody. Using laser confocal fluorescence microscopy, normal erythroid precursors show no alpha globin chain accumulation and exhibited uniformly smooth rim fluorescence of the three membrane proteins. In some thalassemic precursors, spectrin appeared to interact with large alpha globin accumulations, and in many of these cells the spectin appeared clumped and discontinuous. Band 4.1 interacted strongly with accumulations of alpha globin in thalassemic precursors to produce bizarrely clumped zones of abnormal band 4.1 distribution. Band 3 was incorporated smoothly into thalassemic erythroblast membranes. However, the proerythroblasts and basophilic erythroblasts were significantly deficient in band 3. Thus, accumulations of alpha globin in beta- thalassemia major colocalized with and disrupt band 4.1 and spectrin assembly into the membrane. The cause of deficient band 3 incorporation into thalassemic proerythroblast membranes remains unknown. These profound membrane alterations would likely contribute to the intramedullary lysis seen in Cooley's anemia. 相似文献
779.
780.
Parotid masses: MR imaging 总被引:10,自引:0,他引:10
Over a 2-year period 20 patients who presented with masses in the parotid gland were evaluated with magnetic resonance (MR) imaging. T1-weighted images were obtained on a high-resolution, thin-section MR imaging system. When "cystic-appearing" lesions were found, T2-weighted images were obtained in order to better characterize the tumor. As in other areas of the body, MR images of parotid tumors are not usually histologically specific. MR findings may be distinctive in rare cases and define the internal architecture of complex parotid masses. Although poor tumor margination was a clue to malignancy, this was not a consistent finding. The real advantage of MR imaging in evaluating parotid masses was its ability to accurately reveal the extraparotid or intraparotid location of a tumor and demonstrate the relationship of the tumor to the facial nerve. Small and medium-sized mass lesions could be seen as superficial or deep to the facial nerve. Larger masses producing some distortion of the normal course of the nerve made identification of the nerve more difficult, if not impossible. In malignant tumors with gross invasion of the facial canal, MR images can show the extent of nerve involvement. 相似文献