全文获取类型
收费全文 | 2532篇 |
免费 | 133篇 |
国内免费 | 6篇 |
学科分类
医药卫生 | 2671篇 |
出版年
2023年 | 6篇 |
2022年 | 9篇 |
2021年 | 45篇 |
2020年 | 29篇 |
2019年 | 30篇 |
2018年 | 50篇 |
2017年 | 44篇 |
2016年 | 60篇 |
2015年 | 62篇 |
2014年 | 108篇 |
2013年 | 93篇 |
2012年 | 135篇 |
2011年 | 160篇 |
2010年 | 108篇 |
2009年 | 91篇 |
2008年 | 195篇 |
2007年 | 199篇 |
2006年 | 176篇 |
2005年 | 195篇 |
2004年 | 150篇 |
2003年 | 162篇 |
2002年 | 133篇 |
2001年 | 33篇 |
2000年 | 17篇 |
1999年 | 28篇 |
1998年 | 20篇 |
1997年 | 29篇 |
1996年 | 36篇 |
1995年 | 25篇 |
1994年 | 18篇 |
1993年 | 18篇 |
1992年 | 15篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 12篇 |
1987年 | 11篇 |
1986年 | 14篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 10篇 |
1982年 | 15篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 6篇 |
1978年 | 9篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1973年 | 7篇 |
1971年 | 6篇 |
排序方式: 共有2671条查询结果,搜索用时 125 毫秒
31.
32.
Qing-Yi Lu Yu-Sheng Jin Allan Pantuck Zuo-Feng Zhang David Heber Arie Belldegrun Mai Brooks Robert Figlin Jianyu Rao 《Clinical cancer research》2005,11(4):1675-1683
Alteration of actin polymerization and loss of actin filaments is a marker of cellular dedifferentiation and early malignant transformation. To study this phenomenon, an in vitro human urothelial model consisting of two cell lines, HUC-PC and MC-T11, were incorporated into the study design. These two cell lines have different malignant transformation potential. The effect of green tea extract (GTE), a potential anticancer agent, on actin remodeling was investigated. Upon exposure to the carcinogen 4-aminobiphenyl (4-ABP), the untransformed HUC-PC undergoes malignant transformation whereas the transformed MC-T11 progresses from noninvasive to invasive tumor. GTE induces actin polymerization in MC-T11 cells in a dose-responsive manner, but this effect is less obvious in the untransformed, more differentiated HUC-PC cells, which natively have higher actin polymerization status. In contrast, GTE antagonizes carcinogen 4-ABP induced actin depolymerization and stress fiber disruption in HUC-PC cells. In MC-T11 cells, GTE inhibits 4-ABP induced motility by increasing cell adhesion and focal adhesion complex formation. The effect of GTE on actin remodeling seems to be mediated by the stimulation of small GTP-binding protein Rho activity, because C3 exoenzyme, a specific inhibitor for Rho, blocks GTE-mediated Rho activation and stress fiber formation in MC-T11 cells. This study shows that GTE exerts an effect on cytoskeletal actin remodeling and provides further support for the use of GTE as a chemopreventive agent. 相似文献
33.
Pang-Hsien Tu Caterina Giannini Alexander R Judkins Jason M Schwalb Richard Burack Brian P O'Neill Anthony T Yachnis Peter C Burger Bernd W Scheithauer Arie Perry 《Journal of clinical oncology》2005,23(24):5718-5727
PURPOSE: Although rare overall, marginal zone B-cell lymphoma (MZBCL) is the most common primary low-grade CNS lymphoma reported in the literature. The aim of this study is to elucidate the biology and genetic features of this unusual tumor. PATIENTS AND METHODS: Fifteen CNS MZBCLs were studied clinically, pathologically, and genetically, including fluorescent in situ hybridization analyses with commercially available MALT1 and IgH break-apart and centromere 3, 7, 12, and 18 probes. RESULTS: CNS MZBCLs preferentially affect middle-aged women (female-to-male ratio, 4:1), with 93% presenting as dural-based masses mimicking meningioma. Ten patients with 1 to 7.6 years of follow-up after diagnosis showed no evidence of disease after radiation and/or chemotherapy. Like MZBCLs outside of the CNS, they consisted of CD20+, CD3- small B lymphocytes with varying degrees of plasmacytic differentiation and predominantly kappa light-chain restriction (78%). Lymphoid follicles with follicular colonization were seen in three patients and deposition of amyloid was noted in samples from two patients, one of which was tumefactive. Neither Bcl-6 protein nor Epstein-Barr virus-encoded RNA was expressed. Trisomy 3 was detected in six of 12 patients, with no rearrangements of MALT1 or IgH and no trisomies of 7, 12, or 18 detected. CONCLUSION: Our data suggest that intracranial MZBCL is an indolent primary CNS lymphoma that typically presents as a meningioma-like dural-based mass. Trisomy 3, but not MALT1 or IgH translocation, is a common genetic abnormality that may contribute to the pathogenesis of this CNS lymphoma. 相似文献
34.
Arie Erman Semyon Veksler Uzi Gafter Geoffrey Boner Clara Wittenberg David Jonathan van Dijk 《Journal of the renin-angiotensin-aldosterone system》2004,5(3):146-151
INTRODUCTION: Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor beta 1 (TGF-beta 1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-beta 1 in diabetic rats. MATERIALS AND METHODS: Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days. RESULTS: Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-beta1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-beta 1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558). CONCLUSIONS: Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-beta 1. 相似文献
35.
36.
Matthew D. Cykowski Richard A. Allen Angela C. Kanaly Kar-Ming Fung Roxanne Marshall Arie Perry Ethan D. Stolzenberg S. Terence Dunn 《Journal of neuro-oncology》2013,115(3):477-486
Rare pilocytic astrocytomas (PA) have atypical histologic and clinicoradiologic features that raise the differential diagnosis of glioblastoma. Whether ancillary studies can supplement histopathologic examination in placing these cases accurately on the spectrum of WHO Grade I PA to higher-grade glioma is not always clear, partly because these cases are not common. Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations. Ki-67, p53, and p16 protein expression were also examined by immunohistochemistry. BRAF–KIAA1549 fusion status was assessed in the PA subgroup. The rate of BRAF–KIAA1549 fusion was high in these PAs (5/7 tumors) including four extracerebellar examples. A single BRAF V600E mutation was identified in the fusion-negative extracerebellar PA of a very young child who succumbed to the disease. TP53 mutations were present only in malignant gliomas, including three pGBMs and one case designated as PA with anaplastic features (with consultation opinion of pGBM). IDH1 and IDH2 were wild type in all cases, consistent with earlier findings that IDH mutations are not typical in high-grade gliomas of patients ≤14 years of age. Immunohistochemical studies showed substantial overlap in Ki-67 labeling indices, an imperfect correlation between p53 labeling and TP53 mutation status, and complete p16 loss in only two pGBMs but in no PAs. These results suggest that (a) BRAF–KIAA1549 fusion may be common in PAs with atypical clinicoradiologic and histologic features, including those at extracerebellar sites, (b) BRAF V600E mutation is uncommon in extracerebellar PAs, and (c) TP53 mutation analysis remains a valuable tool in identifying childhood gliomas that will likely behave in a malignant fashion. 相似文献
37.
Dani?lle Horst Ruben J. Geerdink Anna M. Gram Arie J. Stoppelenburg Maaike E. Ressing 《Viruses》2012,4(10):2379-2399
The immune system plays a major role in protecting the host against viral infection. Rapid initial protection is conveyed by innate immune cells, while adaptive immunity (including T lymphocytes) requires several days to develop, yet provides high specificity and long-lasting memory. Invariant natural killer T (iNKT) cells are an unusual subset of T lymphocytes, expressing a semi-invariant T cell receptor together with markers of the innate NK cell lineage. Activated iNKT cells can exert direct cytolysis and can rapidly release a variety of immune-polarizing cytokines, thereby regulating the ensuing adaptive immune response. iNKT cells recognize lipids in the context of the antigen-presenting molecule CD1d. Intriguingly, CD1d-restricted iNKT cells appear to play a critical role in anti-viral defense: increased susceptibility to disseminated viral infections is observed both in patients with iNKT cell deficiency as well as in CD1d- and iNKT cell-deficient mice. Moreover, viruses have recently been found to use sophisticated strategies to withstand iNKT cell-mediated elimination. This review focuses on CD1d-restricted lipid presentation and the strategies viruses deploy to subvert this pathway. 相似文献
38.
39.
40.