全文获取类型
收费全文 | 644篇 |
免费 | 43篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 41篇 |
妇产科学 | 3篇 |
基础医学 | 71篇 |
口腔科学 | 12篇 |
临床医学 | 65篇 |
内科学 | 123篇 |
皮肤病学 | 16篇 |
神经病学 | 31篇 |
特种医学 | 117篇 |
外科学 | 36篇 |
综合类 | 106篇 |
预防医学 | 28篇 |
眼科学 | 5篇 |
药学 | 18篇 |
中国医学 | 1篇 |
肿瘤学 | 21篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 8篇 |
2016年 | 9篇 |
2015年 | 18篇 |
2014年 | 25篇 |
2013年 | 16篇 |
2012年 | 25篇 |
2011年 | 14篇 |
2010年 | 31篇 |
2009年 | 33篇 |
2008年 | 34篇 |
2007年 | 25篇 |
2006年 | 19篇 |
2005年 | 13篇 |
2004年 | 10篇 |
2003年 | 10篇 |
2002年 | 12篇 |
2001年 | 15篇 |
2000年 | 8篇 |
1999年 | 15篇 |
1998年 | 47篇 |
1997年 | 40篇 |
1996年 | 32篇 |
1995年 | 19篇 |
1994年 | 27篇 |
1993年 | 22篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 25篇 |
1986年 | 8篇 |
1985年 | 12篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 14篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 1篇 |
1978年 | 8篇 |
1977年 | 4篇 |
1976年 | 8篇 |
1975年 | 5篇 |
1967年 | 1篇 |
排序方式: 共有702条查询结果,搜索用时 20 毫秒
161.
Discrepancy between IIA phenotype and IIB genotype in a patient with a variant of von Willebrand disease 总被引:1,自引:0,他引:1
Ribba AS; Christophe O; Derlon A; Cherel G; Siguret V; Lavergne JM; Girma JP; Meyer D; Pietu G 《Blood》1994,83(3):833-841
Type IIA and IIB von Willebrand disease (vWD) result from qualitative abnormalities of von Willebrand factor (vWF) characterized by an absence in plasma of high molecular weight vWF multimers and an abnormal reactivity of vWF towards platelet glycoprotein (GP) Ib, which is decreased in type IIA and increased in type IIB. In this report, we describe the case of a patient having a IIA vWD phenotype associated with an intermittent thrombocytopenia atypical in this subtype but observed in type IIB vWD. The patient plasma vWF showed an absence of high molecular weight and intermediate multimers and had a decreased binding capacity to GPIb. The affinity of botrocetin was normal for plasma vWF from the propositus. Analysis of the propositus vWF gene showed the presence of a substitution Val 551 to Phe of the mature vWF subunit. This mutation is localized within a 509-695 disulphide loop of the vWF that plays an important role in the binding to GPIb and is where most of the molecular defects described so far were associated with type-IIB vWD. We have reproduced the Val 551 Phe substitution onto the vWF cDNA, expressed it in COS-7 cells, and performed structural and functional analysis of the mutant recombinant protein (rvWFPhe 551). The rvWFPhe 551 had a normal multimeric structure and showed the capacity to spontaneously interact with GPIb. Botrocetin had a decreased affinity for rvWFPhe 551. In conclusion, the Val 551 Phe mutation modifies the affinity of vWF for platelet GPIb, as does a type IIB mutation, and may be responsible for the thrombocytopenia of the patient and the clearance of the high molecular weight and intermediate- sized multimers of vWF from the plasma. The study of the rvWFPhe 551 has confirmed the discrepancy between the IIA phenotype and the IIB genotype of the patient. 相似文献
162.
Gribben JG; Neuberg D; Freedman AS; Gimmi CD; Pesek KW; Barber M; Saporito L; Woo SD; Coral F; Spector N 《Blood》1993,81(12):3449-3457
Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, then therapy could be altered based upon the detection of these cells. The t(14;18) can be detected by polymerase chain reaction (PCR) amplification in 50% of patients with B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in up to 1 million normal cells. To determine the clinical significance of the detection of minimal residual lymphoma cells in the bone marrow (BM) PCR amplification was used to detect the presence of residual lymphoma cells after autologous BM transplantation (ABMT) in serial BM samples from 134 patients with B-cell lymphoma in whom a bcl- 2 translocation could be detected. PCR analysis was performed on a total of 542 BM samples obtained while these patients were in complete remission. Disease-free survival was markedly increased in patients with no PCR-detectable lymphoma cells in the marrow compared with those in whom residual lymphoma cells were detected (P < .00001), and the presence of detectable lymphoma cells was associated with a 48-fold increase in the risk of relapse. Of the 77 patients (57%) with no PCR- detectable lymphoma cells in their most recent BM sample, none have relapsed. In contrast, all 33 patients (25%) who have relapsed had PCR- detectable lymphoma cells detected in their BM before clinical relapse occurred. In 19 patients (14%), residual lymphoma cells in the BM were detected early following transplantation and subsequently were no longer detectable, although these patients received no further therapy. In these patients, residual lymphoma cells may already have been irreversibly damaged by the high-dose therapy or an endogenous immune mechanism may be capable of eliminating residual lymphoma cells in some patients. Therefore, although the detection of minimal residual disease by PCR following ABMT in patients with lymphoma identifies those patients at high risk of relapse, the presence of residual minimal disease early after transplantation may not be associated with poor prognosis in a small subset of patients. Confirmatory studies will be required to determine more definitively the role of minimal disease detection to identify which patients require additional therapy. 相似文献
163.
Szilvassy SJ; Weller KP; Lin W; Sharma AK; Ho AS; Tsukamoto A; Hoffman R; Leiby KR; Gearing DP 《Blood》1996,87(11):4618-4628
Attempts to maintain or expand primitive hematopoietic stem cells in vitro without the concomitant loss of their differentiative and proliferative potential in vivo have largely been unsuccessful. To investigate this problem, we compared the ability of three cloned bone marrow (BM) stromal cell lines to support the growth of primitive Thy- 1lo Sca-1+H-2Khi cells isolated by fluorescence-activated cell sorting from the BM of Ly-5.2 mice treated 1 day previously with 5-fluo- rouracil. Sorted cells were highly enriched in cobblestone area-forming cells (CAFC), but their frequency was dependent on the stromal cell lines used in this assay (1 per 45 cells on SyS-1; 1 per 97 cells on PA6). In the presence of recombinant leukemia inhibitory factor (LIF), CAFC cloning efficiency was increased to 1 per 8 cells on SyS-1 and 1 per 11 cells on PA6, thus showing the high clonogenicity of this primitive stem cell population. More primitive stem cells with competitive repopulating potential were measured by injecting the sorted cells into lethally irradiated Ly-5.1 mice together with 10(5) radioprotective Ly-5.1 BM cells whose long-term repopulating ability has been "compromised" by two previous cycles of marrow transplantation and regeneration. Donor-derived lymphocytes and granulocytes were detected in 66% of animals injected with 50 sorted cells. To quantitate the maintenance of competitive repopulating units (CRU) by stromal cells, sorted cells were transplanted at limiting dilution before and after being cultured for 2 weeks on adherent layers of SyS-1, PA6, or S17 cells. CRU represented 1 per 55 freshly sorted cells. CRU could be recovered from cocultures supported by all three stromal cell lines, but their numbers were approximately-sevenfold less than on day 0. In contrast, the addition of LIF to stromal cultures improved CRU survival by 2.5-fold on S17 and PA6 cells (approximately two-fold to threefold decline), and enabled their maintenance on SyS-1. LIF appeared to act indirectly, because alone it did not support the proliferation of Thy- 1lo Sca-1+H-2Khi cells in stroma-free cultures. Polymerase chain reaction (RT-PCR) analysis revealed that Interleukin-1beta (IL-1 beta) IL-2, IL-6, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, transforming growth factors, LIF, and Steel Factor (SLF) mRNAs were upregulated in SyS-1 within 1 to 6 hours of LIF-stimulation. To determine if increased expression of SLF by LIF-stimulated SyS-1 cells could account for their capacity to support stem cells, sorted calls were cocultured on simian CV-E cells that were transfected with an expression vector encoding membrane-bound SLF, or supplemented with soluble SLF. In both cases, SLF synergized with IL-6 produced endogenously by CV-E cells enabling CAFC growth equivalent to that on LIF-stimulated SyS-1. CAFC development on LIF- stimulated SyS-1 could also be completely abrogated by an anti-SLF antibody. These data provide evidence for a role of LIF in the support of long-term repopulating stem cells by indirectly promoting cytokine expression by BM stroma. Furthermore, we have used quantitative assays to show a maintenance of CRU numbers, with retention of in vivo function following ex vivo culture. 相似文献
164.
Characterization of a new non-Hodgkin's lymphoma cell line (NCEB-1) with a chromosomal (11:14) translocation [t(11:14)(q13;q32)] 总被引:2,自引:2,他引:2
Saltman DL; Cachia PG; Dewar AE; Ross FM; Krajewski AS; Ludlam C; Steel CM 《Blood》1988,72(6):2026-2030
A new cell line, NCEB-1, was established by Epstein-Barr virus (EBV) transformation of peripheral blood mononuclear cells from a patient with centroblastic-centrocytic diffuse lymphoma expressing IgM lambda. The transformed cells were lymphoblastoid, with many cells showing a plasmacytoid morphology. The NCEB-1 cells had cytoplasmic Ig (CyIg), with loss of the surface Ig (SIg) expression. Cytogenetic analysis of the cell line demonstrated two clones with variations: a hypodiploid clone, with a complex karyotype including a t(11;14)(q13;q32) similar to the original tumor cells, and a near tetraploid clone with the same markers. Southern blot analysis of DNA from the patient's neoplastic cells and NCEB-1 demonstrated identical Ig heavy chain gene rearrangement, confirming the origin of the cell line. The cell line was not tumorigenic when tested in an in vitro assay using immunosuppressed mice. NCEB-1 has been in continuous culture for 9 months and will be valuable for the in vivo study of non-Hodgkin's lymphoma and EBV transformation. 相似文献
165.
166.
167.
Vitamin D and/or calcium deficient diets may differentially affect muscle fiber neuromuscular junction innervation
下载免费PDF全文
![点击此处可从《Muscle & nerve》网站下载免费的PDF全文](/ch/ext_images/free.gif)
David J. Gifondorwa PhD Tyran D. Thompson BS June Wiley BS Alexander E. Culver BS Pamela K. Shetler AS Guilherme V. Rocha PhD Yanfei L. Ma MD Venkatesh Krishnan PhD Henry U. Bryant PhD 《Muscle & nerve》2016,54(6):1120-1132
Introduction: There is evidence that supports a role for Vitamin D (Vit. D) in muscle. The exact mechanism by which Vit. D deficiency impairs muscle strength and function is not clear. Methods: Three‐week‐old mice were fed diets with varied combinations of Vit. D and Ca2+ deficiency. Behavioral testing, genomic and protein analysis, and muscle histology were performed with a focus on neuromuscular junction (NMJ) ‐related genes. Results: Vit. D and Ca2+ deficient mice performed more poorly on given behavioral tasks than animals with Vit. D deficiency alone. Genomic and protein analysis of the soleus and tibialis anterior muscles revealed changes in several Vit. D metabolic, NMJ‐related, and protein chaperoning and refolding genes. Conclusions: These data suggest that detrimental effects of a Vit. D deficient or a Vit. D and Ca2+ deficient diet may be a result of differential alterations in the structure and function of the NMJ and a lack of a sustained stress response in muscles. Muscle Nerve 54 : 1120–1132, 2016 相似文献
168.
169.
Rabinowe SN; Neuberg D; Bierman PJ; Vose JM; Nemunaitis J; Singer JW; Freedman AS; Mauch P; Demetri G; Onetto N 《Blood》1993,81(7):1903-1908
One hundred and twenty-eight patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and acute lymphoblastic leukemia (ALL) previously reported from a phase III trial of rhGM-CSF or placebo following autologous bone marrow transplantation (ABMT) were investigated for the development of late toxicities. Median follow-up is 36 months. No apparent long-term deleterious effects on BM function were observed. Moreover, disease-free survival and overall survival were similar for patients on both treatment arms, arguing for the long- term safety of recombinant human granulocyte macrophage-colony- stimulating factor (rhGM-CSF). The only factors predictive for both a high risk of relapse over time and mortality were having the diagnosis of ALL and/or undergoing ABMT in resistant relapse. We attempted to identify clinical variables before BM harvest, at the time of marrow infusion, or events within the first 100 days posttransplant, which might predict speed of neutrophil recovery in the setting of placebo or rhGM-CSF administration after ABMT. Only previous exposure to agents that deplete stem cells led to a significant delay in neutrophil recovery, suggesting their avoidance in patients who may undergo ABMT. Nevertheless, even those patients benefited from rhGM-CSF. For all patients, rhGM-CSF and agents that deplete stem cells were the strongest independent predictors for neutrophil engraftment. With the increasing use of newer hematopoietic growth factors both alone and in combination, long-term follow-up is essential to confirm the same safety that we report with rhGM-CSF. 相似文献
170.
N Hudson AS Taha RI Russell P Trye J Cottrell SG Mann AJ Swanell RD Sturrock CJ Hawkey 《Gastroenterology》1997,112(6):1817-1822
BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulceration. How to manage patients with NSAID-associated ulcers is a common clinical dilemma. High-dose famotidine in the healing and maintenance of NSAID-associated gastroduodenal ulceration was therefore evaluated. METHODS: One hundred four patients with rheumatoid or osteoarthritis who had gastroduodenal ulceration received famotidine, 40 mg twice daily. Sixteen patients stopped and 88 continued their NSAID treatment. Ulcer healing was assessed endoscopically at 4 and 12 weeks. Seventy-eight NSAID users with healed ulcers were then randomized to receive 40 mg twice daily famotidine or placebo and underwent endoscopy at 4, 12, and 24 weeks. RESULTS: Cumulative ulcer healing rates at 12 weeks were 89.0% (95% confidence interval [CI], 82.3%-95.7%) for patients who continued NSAID treatment and 100% (95% CI, 82.9%-100.0%) for those who stopped. The subsequent estimated cumulative gastroduodenal ulcer relapse over 6 months for NSAID users who took placebo was 53.5% (95% CI, 36.6%- 70.3%). This was reduced to 26.0% (12.1%-39.9%) in patients taking famotidine (P = 0.011). CONCLUSIONS: High-dose famotidine is effective ulcer healing therapy in patients who stop or continue NSAID treatment and significantly reduced the cumulative incidence of gastroduodenal ulcer recurrence compared with placebo when given as maintenance therapy. (Gastroenterology 1997 Jun;112(6):1817-22) 相似文献