全文获取类型
收费全文 | 356篇 |
免费 | 26篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 21篇 |
妇产科学 | 5篇 |
基础医学 | 52篇 |
口腔科学 | 18篇 |
临床医学 | 40篇 |
内科学 | 68篇 |
皮肤病学 | 18篇 |
神经病学 | 19篇 |
特种医学 | 36篇 |
外科学 | 39篇 |
综合类 | 16篇 |
预防医学 | 18篇 |
眼科学 | 6篇 |
药学 | 22篇 |
肿瘤学 | 8篇 |
出版年
2021年 | 3篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 8篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 12篇 |
2013年 | 26篇 |
2012年 | 14篇 |
2011年 | 11篇 |
2010年 | 17篇 |
2009年 | 26篇 |
2008年 | 18篇 |
2007年 | 10篇 |
2006年 | 13篇 |
2005年 | 19篇 |
2004年 | 6篇 |
2003年 | 7篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 9篇 |
1999年 | 2篇 |
1998年 | 18篇 |
1997年 | 22篇 |
1996年 | 20篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 4篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 1篇 |
排序方式: 共有395条查询结果,搜索用时 15 毫秒
41.
RM Nobre ALR Ribeiro SM Alves-Junior FM Tuji M das G Rodrigues Pinheiro LR Pinheiro JJV Pinheiro 《Dento maxillo facial radiology》2012,41(7):541-547
Objectives
A wide variety of manifestations is presented in patients with Gaucher''s disease (GD), including bone, haematology and visceral disturbances. This study was conducted to ascertain the main maxillofacial abnormalities by means of clinical survey, panoramic and cone beam CT (CBCT); to compare the patient''s group with an age–sex matched control group; and to correlate clinical and radiological data.Methods
Ten patients previously diagnosed with GD were submitted to clinical and radiological surveys (CBCT and panoramic radiographs). The examination consisted of anamnesis, extra- and intraoral examinations and analyses of each patient''s records. Imaging data were collected from the point of view of 3 observers, and the results compared with a healthy group (20 individuals) by means of statistical analysis (Fisher''s exact test).Results
Gaucher patients had significantly more manifestations than otherwise healthy carriers. The most prevalent findings were enlarged marrow spaces, generalized osteopenia and effacement of jaw structures (mandibular canal, lamina dura and mental foramen). Here we describe a case in which thickening of the maxillary sinus mucosa was observed on CBCT rather than opacification of the sinus as seen on panoramic radiographs. Pathological fractures, root resorption and delay on tooth eruption were not observed.Conclusions
A poor relationship could be observed between clinical and radiological data. Patients showed important bone manifestations, which require careful diagnostic and surgical planning whenever necessary. Although panoramic radiographs have shown significant differences, CBCT is more effective in pointing out differences between patients and a control group, thus showing it as an important tool for evaluation of Gaucher patients. 相似文献42.
Leukemic cell growth in SCID mice as a predictor of relapse in high- risk B-lineage acute lymphoblastic leukemia 总被引:3,自引:2,他引:3
Uckun FM; Sather H; Reaman G; Shuster J; Land V; Trigg M; Gunther R; Chelstrom L; Bleyer A; Gaynon P 《Blood》1995,85(4):873-878
Mice with severe combined immunodeficiency (SCID) provide a model system to examine the in vivo homing, engraftment, and growth patterns of normal and malignant human hematopoietic cells. The relation between leukemic cell growth in this model and the treatment outcome in patients from whom cells were derived has not been established. Leukemic cells from 42 children with newly diagnosed high-risk B- lineage acute lymphoblastic leukemia were inoculated intravenously into CB.17 SCID mice. Mice were killed at 12 weeks or when they became moribund as a result of disseminated leukemia. All mice were necropsied and subjected to a series of laboratory studies to assess their burden of human leukemic cells. Twenty-three patients whose leukemic cells caused histopathologically detectable leukemia in SCID mice had a significantly higher relapse rate than the 19 patients whose leukemic cells did not (estimated 5-year event-free survival: 29.5% v 94.7%; 95% confidence intervals, 11.2% to 50.7% v 68.1% to 99.2%; P < .0001 by log- rank test). The occurrence of overt leukemia in SCID mice was was a highly significant predictor of patient relapse. The estimated instantaneous risk of relapse for patients whose leukemic cells caused overt leukemia in SCID mice was 21.5-fold greater than that for the remaining patients. Thus, growth of human leukemic cells in SCID mice is a strong and independent predictor of relapse in patients with newly diagnosed high-risk B-lineage acute lymphoblastic leukemia. 相似文献
43.
Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation 总被引:2,自引:0,他引:2
Bertram JH; Gill PS; Levine AM; Boquiren D; Hoffman FM; Meyer P; Mitchell MS 《Blood》1986,68(3):752-761
Eight patients with cutaneous T cell lymphomas (CTCL) and five with various other T cell malignancies were treated with mouse monoclonal antibody (MoAb) T101. Doses of 1 to 500 mg were administered weekly over a two-hour period and resulted in one complete remission (convoluted T cell lymphoma) and one partial remission (CTCL). Remission duration was 6 weeks and 3 months, respectively. Frequent toxicities were pruritus, hives, flushing, and shortness of breath. Supraventricular arrhythmias and blood pressure instability were also observed. Complete targeting of peripheral blood T cells was achieved with 1 mg of MoAb in the nonleukemic patients (WBC less than 10,000/microL), and free, bioavailable antibody was present at the next (10-mg) dose level. Even higher doses resulted in substantial antibody excess that persisted for as long as 6 weeks. Serum concentrations of MoAb decreased with increasing number of peripheral blood T cells, and 25 to 35 mg of T101 were required for induction of antibody excess in leukemic patients. Excess antibody induced antigenic modulation, which was of consequence only if MoAb excess persisted to the next treatment. In the original treatment, the rapidly administered MoAb was able to target and remove peripheral blood T cells before the development of antigenic modulation. Antimouse antibodies developed in three patients. Their presence rendered further therapy ineffective and was associated with an anaphylactic reaction in one patient. Development of these antibodies could not be predicted by lymphoproliferative assays. In these assays, however, the T101 protein strongly stimulated the mononuclear cells of the patient who reached the only complete remission of this trial. Immunologic stimulation by the MoAb thus might have played a role in this patient's antitumor response. In summary, therapy with MoAb T101 was specific but only modestly efficacious. Rapid infusion of nonmodulating doses of antibody provided excellent targeting and removal of peripheral blood T cells and might be a valid approach in future trials with immunoconjugated T101. 相似文献
44.
Brennan FM; Browne KA; Green PA; Jaspar JM; Maini RN; Feldmann M 《Rheumatology (Oxford, England)》1997,36(6):643-650
Matrix metalloproteinase (MMP)-1 and MMP-3 levels were measured in serum
samples from rheumatoid arthritis (RA) patients undergoing a double-blinded
placebo-controlled trial with the chimaeric anti-tumour necrosis factor
(TNF)-alpha antibody cA2. Both MMP-1 (P < 0.015), but to a larger extent
MMP-3 (P < 0.001) levels were elevated in all RA patients prior to the
commencement of the trial compared with normal control sera. Following cA2
therapy, MMP-1 and MMP-3 levels were assessed in the placebo, and 1 and 10
mg/kg cA2-treated groups at 7, 14, 21 and 28 days. In both the 1 and the 10
mg/kg cA2-treated groups, a significant decrease in serum MMP-3 levels at
all time points was observed, reducing maximally to 41% of pre-infusion
values at day 7. MMP-1 levels were also reduced, but less dramatically than
MMP-3, to 85% of pre-infusion values after 14 days in the 10 mg/kg cA2
treated group. In a separate non-placebo-controlled study, we also
evaluated the tissue inhibitor of metalloproteinase (TIMP)-1 levels in
plasma following cA2 infusion. Pre-infusion TIMP-1 levels were above the
normal control range, but were significantly reduced (P < 0.035) 14 days
after infusion to 72% of pre-infusion values. This study confirms previous
reports that MMP-3 levels are elevated and correlate with measures of
inflammation in RA, and furthermore demonstrate that serum MMP-3 and MMP-1
levels are downmodulated following anti-TNF-alpha antibody therapy. Whilst
serum MMP-3 levels correlated with C-reactive protein (CRP) both prior to
and following anti-TNF-alpha antibody therapy, it remains to be
demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and
bone resorptive processes which are evident in this disease.
相似文献
45.
运用Ca2+指示剂Fura-2作为细胞内钙离子的荧光探针,利用AR—CM—MIC阳离子测定系统,检测了分离的神经细胞内游离钙及其变化,并观测了DGAVP和Org2766对蛋白质合成抑制剂茴香霉素(ANI)引起细胞内钙离子浓度([Ca2+]i)变化的影响。结果表明茴香霉素可使[Ca2+]i显著升高,且有量效关系;DGAVP本身并不引起[Ca2+]i发生显著变化,但适当剂量的DGAVP可显著对抗一定剂量范围内ANI升高[Ca2+]i的作用,提示DGAVP对抗ANI的蛋白质合成抑制效应可能是通过拮抗ANI升高[Ca2+]i这一途径实现的,另一神经肽Org2766则可能不是通过这一机制发生作用。从细胞内Ca2+的角度看,这两种肽的作用机理显然是不同的。 相似文献
46.
Robertson RT; Gallardo KA; Claytor KJ; Ha DH; Ku KH; Yu BP; Lauterborn JC; Wiley RG; Yu J; Gall CM; Leslie FM 《Cerebral cortex (New York, N.Y. : 1991)》1998,8(2):142-155
The role of basal forebrain-derived cholinergic afferents in the
development of neocortex was studied in postnatal rats. Newborn rat pups
received intraventricular injections of 192 IgG-saporin. Following survival
periods ranging from 2 days to 6 months, the brains were processed to
document the cholinergic lesion and to examine morphological consequences.
Immunocytochemistry for choline acetyltransferase (ChAT) and in situ
hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the
cholinergic neurons in the medial septum and nucleus of the diagonal band
of Broca in the basal forebrain. In situ hybridization for glutamic acid
decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons.
Acetylcholinesterase histochemistry demonstrates a marked reduction of the
cholinergic axons in neocortex. Cholinergic axons are reduced throughout
the cortical layers; this reduction is more marked in medial than in
lateral cortical areas. The thickness of neocortex is reduced by
approximately 10%. Retrograde labeling of layer V cortico-collicular
pyramidal cells reveals a reduction in cell body size and also a reduction
in numbers of branches of apical dendrites. Spine densities on apical
dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated
cases; no change was detected in number of spines on basal dendrites. These
results indicate a developmental or maintenance role for cholinergic
afferents to cerebral cortical neurons.
相似文献
47.
48.
Capsular visualization in lipohemarthrosis of the knee 总被引:1,自引:0,他引:1
49.
I. Vercruysse AM Vermeulen FM Belpaire DL Massart and AG Dupont 《Fundamental & clinical pharmacology》1994,8(4):373-378
Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age. 相似文献
50.
Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine hematopoietic progenitors 总被引:1,自引:0,他引:1
Salachas F; Schneider E; Lemoine FM; Lebel B; Daeron M; Navarro S; Ziltener H; Dy M 《Blood》1994,84(4):1098-1107
Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE. 相似文献