全文获取类型
收费全文 | 1593篇 |
免费 | 92篇 |
国内免费 | 82篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 76篇 |
妇产科学 | 12篇 |
基础医学 | 175篇 |
口腔科学 | 27篇 |
临床医学 | 263篇 |
内科学 | 365篇 |
皮肤病学 | 102篇 |
神经病学 | 36篇 |
特种医学 | 305篇 |
外科学 | 139篇 |
综合类 | 30篇 |
预防医学 | 48篇 |
眼科学 | 6篇 |
药学 | 83篇 |
肿瘤学 | 95篇 |
出版年
2023年 | 4篇 |
2022年 | 9篇 |
2021年 | 19篇 |
2020年 | 16篇 |
2019年 | 32篇 |
2018年 | 25篇 |
2017年 | 22篇 |
2016年 | 25篇 |
2015年 | 24篇 |
2014年 | 27篇 |
2013年 | 44篇 |
2012年 | 27篇 |
2011年 | 37篇 |
2010年 | 70篇 |
2009年 | 64篇 |
2008年 | 49篇 |
2007年 | 79篇 |
2006年 | 35篇 |
2005年 | 49篇 |
2004年 | 36篇 |
2003年 | 26篇 |
2002年 | 32篇 |
2001年 | 27篇 |
2000年 | 21篇 |
1999年 | 28篇 |
1998年 | 95篇 |
1997年 | 88篇 |
1996年 | 109篇 |
1995年 | 89篇 |
1994年 | 88篇 |
1993年 | 75篇 |
1992年 | 23篇 |
1991年 | 31篇 |
1990年 | 28篇 |
1989年 | 32篇 |
1988年 | 37篇 |
1987年 | 28篇 |
1986年 | 35篇 |
1985年 | 34篇 |
1984年 | 13篇 |
1983年 | 22篇 |
1982年 | 20篇 |
1981年 | 21篇 |
1980年 | 17篇 |
1979年 | 4篇 |
1978年 | 9篇 |
1977年 | 14篇 |
1976年 | 14篇 |
1975年 | 7篇 |
1974年 | 2篇 |
排序方式: 共有1767条查询结果,搜索用时 15 毫秒
61.
Journal of Digital Imaging - Accurate segmentation of a breast tumor region is fundamental for treatment. Magnetic resonance imaging (MRI) is a widely used diagnostic tool. In this paper, a new... 相似文献
62.
63.
Local anesthesia in pediatric dermatologic surgery: Evaluation of a patient‐centered approach 下载免费PDF全文
May El Hachem MD Claudia Carnevale MD Andrea Diociaiuti MD PhD Cristiana De Ranieri PsyD Simona Giancristoforo MD Giovanna Zambruno MD Marta L. Ciofi Degli Atti MD 《Pediatric dermatology》2018,35(1):112-116
Background/Objectives
A few studies have documented the effect of local anesthesia for minor dermatologic surgical procedures on children and their parents. Our objective was to evaluate the psychological effect and global satisfaction of a patient‐centered approach to dermatologic surgery under local anesthesia.Methods
Two self‐administered questionnaires were used to evaluate the distress and global satisfaction of 388 children who underwent dermatologic surgery under local anesthesia, accompanied by oral and written therapeutic education measures (structured information and a cartoon brochure illustrating the procedure) addressed to children and parents. Distraction techniques were also used during the procedures.Results
Although 54.5% of patients manifested some degree of fear, all other parameters analyzed (pain, surgery‐related distress, surgical team–patient and –family relationship, global satisfaction) indicated that the procedures resulted in limited distress and that the large majority of children and parents tolerated them well.Conclusion
Specific measures for therapeutic pediatric patient education may be helpful in limiting discomfort, anxiety, and pain perception linked to procedures performed under local anesthesia. Further controlled studies are required to more precisely assess the benefits of specific therapeutic education measures. 相似文献64.
Granulocyte colony-stimulating factor (G-CSF) induces rapid phosphorylation of JAK kinases as well as activation of the p21ras route through interaction with its specific receptor (G-CSF-R). The cytoplasmic membrane-proximal region of G-CSF-R (amino acids 631 to 684) is necessary for proliferation induction and activation of JAK2. In contrast, activation of Shc and Syp, signaling molecules implicated in the p21ras signaling route, depends on the phosphorylation of tyrosine residues located in the membrane-distal region (amino acids 685 to 813) of G-CSF-R. We investigated whether G-CSF-induced activation of signaling complexes of the p21ras route depends on the function of the membrane-proximal cytoplasmic region of G-CSF-R. A G- CSF-R mutant was constructed in which tryptophan 650 was replaced by arginine and expressed in BAF3 cells (BAF/W650R). In contrast to BAF3 cell transfectants expressing wild-type G-CSF-R, BAF/W650-R cells did not proliferate and did not show activation of JAK2, STAT1, or STAT3 in response to G-CSF. Immunoprecipitations with anti-Shc and anti-Grb2 antisera showed that mutant W650R also failed to activate Syp and Shc. These data indicate that the membrane-proximal cytoplasmic domain of G- CSF-R is not only crucial for proliferative signaling and activation of JAK2 and STATs, but is also required for activation of the p21ras route, which occurs via the membrane-distal region of G-CSF-R. 相似文献
65.
C. Dionisi-Vici L. De Felice M. El Hachem S. Bottero C. Rizzo A. Paoloni B. Goffredo G. Sabetta M. Caniglia 《Journal of inherited metabolic disease》1998,21(2):95-102
In addition to systemic manifestations with skeletal, pulmonary, renal, and haematological signs, lysinuric protein intolerance (LPI), a membrane transport defect of cationic amino acids, is often complicated by severe life-threatening immunological manifestations. A 10-year-old boy with LPI who exhibited a severe systemic immunohaematological disease is described here. This patient showed cutaneous lesions similar to the subacute form of systemic lupus erythematosus, severe anaemia and dysproteinaemia, and a marked reduction of circulating T lymphocytes, mainly the CD4+ cells. In vitro bone marrow cell culture studies showed that addition of patient's serum induced macrophage proliferation and inhibited erythroid progenitor cell growth. Treatment with high-dose intravenous immune globulin resolved most of the clinical and laboratory abnormalities. 相似文献
66.
Lauener RP; Huttner S; Buisson M; Hossle JP; Albisetti M; Seigneurin JM; Seger RA; Nadal D 《Blood》1995,86(4):1400-1407
One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV- infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV- infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome. 相似文献
67.
Effects of interleukin-11 on the proliferation and cell cycle status of myeloid leukemic cells 总被引:1,自引:0,他引:1
Interleukin-11 (IL-11) is a pleiotropic cytokine with effects on many different targets. Within the hematopoietic system, the effects of IL- 11 are largely manifest only through combination with other cytokines, including IL-3 and Steel factor (SF). In the present study, we addressed the question of IL-11 responsiveness within the different types of human leukemic cells, as well as the mechanism of action of IL- 11 at the cellular level. Analysis of a panel of samples from different patients with acute myeloblastic leukemia (AML) and myeloid leukemic cell lines indicated that IL-11 alone was ineffective in supporting myeloid leukemic cell growth but frequently enhanced growth supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or SF. In contrast, three acute pre-B lymphocytic leukemia (pre-B-ALL) and two acute T lymphocytic leukemia (T-ALL) lines failed to respond to IL- 11 alone or when combined with other cytokines. The growth enhancement of IL-11 among the AML patient samples was dose dependent and remarkably constant with half-efficient concentrations in the range of 0.3 to 0.4 ng/mL. The thymidine suicide studies with the patient samples revealed that 40% to 50% of the blast cells were in S-phase when exposed for 16 hours to IL-3 and this level was increased to 70% to 90% in response to either IL-11 or IL-6. Our data suggest that the latter two interleukins act synergistically with the direct mitogenic factor, IL-3, in triggering AML blast-cell proliferation. Detailed analysis with several patient samples further revealed that SF and IL- 11 both enhance IL-3-supported clonogenic growth of AML blasts and the combination of all three growth factors yields optimal growth. In contrast, IL-6 does not further enhance the effect of IL-11. These results indicate that SF and IL-11 enhance IL-3-dependent clonogenic growth through two distinct pathways, whereas IL-6 and IL-11 may trigger the same pathway. 相似文献
68.
Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta 总被引:12,自引:0,他引:12
Farcet JP; Gaulard P; Marolleau JP; Le Couedic JP; Henni T; Gourdin MF; Divine M; Haioun C; Zafrani S; Goossens M 《Blood》1990,75(11):2213-2219
Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells. 相似文献
69.
Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin 总被引:23,自引:3,他引:23
Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation. 相似文献
70.
E J Anaissie R Hachem C Legrand P Legenne P Nelson G P Bodey 《The Journal of infectious diseases》1992,165(6):1155-1157
Systemic fusarial infections have emerged as a significant cause of mortality in cancer patients. Yet, little is known about the management of these infections. The in vivo antifungal activity of amphotericin B in CF1 mice with disseminated fusarial infections was studied. Two pathogenic strains of Fusarium solani were used. Intraperitoneal administration of amphotericin B in daily doses of 0.5, 1, and 2 mg/kg for less than or equal to 10 days did not prolong survival of treated animals. Clearance of F. solani from kidneys was similar in mice treated with 1 mg/kg per day of amphotericin B and in untreated animals. These results are in agreement with the known in vitro and in vivo resistance of Fusarium species to amphotericin B. 相似文献