全文获取类型
收费全文 | 1237篇 |
免费 | 41篇 |
国内免费 | 12篇 |
专业分类
耳鼻咽喉 | 10篇 |
儿科学 | 366篇 |
妇产科学 | 2篇 |
基础医学 | 128篇 |
口腔科学 | 4篇 |
临床医学 | 66篇 |
内科学 | 44篇 |
神经病学 | 104篇 |
特种医学 | 53篇 |
外科学 | 184篇 |
综合类 | 41篇 |
预防医学 | 11篇 |
眼科学 | 4篇 |
药学 | 68篇 |
中国医学 | 3篇 |
肿瘤学 | 202篇 |
出版年
2023年 | 10篇 |
2022年 | 35篇 |
2021年 | 32篇 |
2020年 | 20篇 |
2019年 | 22篇 |
2018年 | 16篇 |
2017年 | 29篇 |
2016年 | 32篇 |
2015年 | 29篇 |
2014年 | 46篇 |
2013年 | 58篇 |
2012年 | 58篇 |
2011年 | 76篇 |
2010年 | 52篇 |
2009年 | 63篇 |
2008年 | 78篇 |
2007年 | 66篇 |
2006年 | 55篇 |
2005年 | 46篇 |
2004年 | 40篇 |
2003年 | 28篇 |
2002年 | 28篇 |
2001年 | 26篇 |
2000年 | 33篇 |
1999年 | 18篇 |
1998年 | 27篇 |
1997年 | 17篇 |
1996年 | 15篇 |
1995年 | 29篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 11篇 |
1991年 | 22篇 |
1990年 | 14篇 |
1989年 | 17篇 |
1988年 | 14篇 |
1987年 | 18篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 13篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有1290条查询结果,搜索用时 15 毫秒
1.
Growth of cultured NlE-115 neuroblastoma cells in 1 μM A23187 for 2 days to elevate internal Ca reduced both membrane Na current and the transient, but not steady state, component of outward K current. Na channel mRNA abundance was reduced by an average value of 45% without effect on Kv3.1. Increases in internal Ca may therefore control excitability by independent regulation of Na and K channel mRNA abundance in neurons. 相似文献
2.
目的探讨成神经细胞瘤骨转移的X线表现及分型。方法分析13例成神经细胞瘤骨转移的X线表现,并根据X线表现将其分为溶骨型和成骨型。结果13例患者中,溶骨型9例,成骨型4例,各型病例均有其特征性的X线表现。结论根据患者年龄及特征性的X线表现,对成神经细胞瘤骨转移可作出诊断。 相似文献
3.
The pathogenesis of diabetic neuropathy is incompletely understood. The possibility that humoral neurotoxic factors contribute as a cause of diabetic neuropathy was tested by application of serum from patients with Type 1 and Type 2 diabetes to mouse neuroblastoma cells, which have the characteristics of adrenergic neurons in culture. Serum from patients with Type 1 diabetes and somatic neuropathy significantly inhibited both proliferation and differentiation of neuroblastoma cells, while serum from patients with Type 1 diabetes but no symptoms of neuropathy and patients with Type 2 diabetes and neuropathy had no effect on proliferation, and serum from Type 2 patients only marginally inhibited differentiation. The effects of Type 1 diabetic serum could be reversed by pre-absorption of the serum to neuroblastoma cells, and were independent of glucose levels. Immunoglobulins precipitated from the sera mimicked the effects of whole sera. These results suggest that Type 1 diabetes mellitus causes a change in serum composition, possibly related to autoimmunity, that is capable of contributing to adrenergic autonomic neuropathy in diabetic patients. 相似文献
4.
Type 1 diabetes is an autoimmune disease resulting in destruction of pancreatic β cells. Many of the pancreatic β cell autoantigens are also neuronal cell components. Using adrenergic neuroblastoma cells, we have previously demonstrated that humoral mechanisms may contribute to the development of diabetic neuropathy in Type 1 patients. We hypothesize that the toxic factor in Type 1 diabetic serum is an immunoglobulin. When neuroblastoma cells were exposed to immunoglobulins precipitated from serum of Type 1 diabetes patients with neuropathy, cell growth was significantly inhibited by day 5 (3.8 ± 2.4 times 105 cells) compared to cells cultured with immunoglobulins from control (8.2 ± 2.3 times 105 cells) or Type 2 diabetic serum (7.0 ± 3.0 times 105 cells). The inhibitory effect (3.2 ± 0.9 times 105 cells) could be removed from Type 1 diabetic serum by affinity precipitation with protein A-agarose (8.0 ± 0.8 times 105 cells). Mild heat denaturing of the serum reversed the inhibitory effect (3.8 ± 0.9 vs 1.4 ± 1.4 times 105 cells), indicating a requirement for complement. Immunofluorescent labelling with anti-IgG secondary antibody of cells exposed to Type 1 diabetic serum indicated recognition of a membrane-bound antigen. The studies in this report support the hypothesis that autoimmune neuronal destruction may contribute to the development of diabetic autonomic neuropathy in patients with Type 1 diabetes. 相似文献
5.
J. M. Maloteaux J. N. Octave E. C. Laterre P. M. Laduron 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(1-2):192-199
Summary There was stereospecific binding of 3H-lofentanil (K
D value = 1.53 nM) to membranes of neuroblastoma-glioma NG 108-15 cells which are known to bear high affinity binding sites for enkephalin derivatives (-opiate receptor subtype). There was no high affinity specific binding of the -opiate specific ligand 3H-sufentanil. The specific binding of 3H-lofentanil to -opiate receptor subtype was down-regulated (decrease in B
max value without change in the K
D value) after prolonged incubation of the cells in the presence of leu- and met- enkephalin (0.1 M). There was no down-regulation of the opiate receptors (3H-lofentanil and 3H-d-ala-d-leu-enkephalin specific binding) after incubation of NG 108-15 cells with drugs from the fentanyl series (alfentanil or sufentanil).In cultured neurones from rat forebrain (15 day old embryos), the 3H-lofentanil binding was specific with high affinity (K
D: 0.048 nM) and a slow dissociation rate similar to that in adult rat cortex. Drugs of the fentanyl series (4-anilino-piperidines) were potent displacers whereas agonists of the - (enkephalin derivatives), (phencyclidine, haloperidol, 3-hydroxyphenyl-propylpiperidine) or K- (U 50488) opiate sites had a low affinity (K
i > 0.5 M) for 3H-lofentanil specific binding sites. Since there was also specific binding of 3H-sufentanil, the opiate receptors in cultured neurones seem to be mainly of the -subtype and this is consistent with the ontogeny of opiate receptors subtypes. These receptors were down-regulated after incubation in the presence of etorphine, sufentanil and alfentanil but not enkephalin derivatives.These results strongly suggest specific binding of 3H-sufentanil and 3H-lofentanil mainly to the so-called -opiate receptors in cultured neurones and a specific binding of 3H-lofentanil to lower affinity -opiate receptors in neuroblastoma-glioma cells. The down-regulation of the -opiate binding sites in cultured neurones and that of the -site in neuroblastoma × glioma hybrid cells were dose-and temperature-dependent, induced by the corresponding high affinity agonists and prevented by naloxone. Morphine did not induce down-regulation of or receptor sites, possibly because of a partial antagonist effect on both receptor subtypes.
Send offprint requests to J. M. Maloteaux at the above address 相似文献
6.
Rhabdomyoblasts demonstrating immunoreactivity for muscle-specific actin, desmin, and myoglobin were identified in smears obtained by aspiration from a large retroperitoneal mass in a 14-mo-old girl. Following a tentative diagnosis of a rhabdomyogenous neoplasm, retroperitoneal exploration and adrenalectomy demonstrated a stromal poor neuroblastoma with extensive rhabdomyogenous differentiation. The presence of a subpopulation of rhabdomyoblasts was not diagnostic of rhabdomyosarcoma when obtained by fine-needle aspiration from a retroperitoneal tumor composed predominantly of primitive small round cells. 相似文献
7.
Béatrice Rouzaire-Dubois Valérie Gérard Jean -Marc Dubois 《Pflügers Archiv : European journal of physiology》1993,423(3-4):202-205
The effects of the flavonoid quercetin on cell proliferation and voltage-dependent K+ current were studied on mouse neuroblastoma×glioma hybrid cells. In the presence of 1 % fetal calf serum, quercetin inhibited both cell proliferation and K+ current with effective doses inducing half-maximum effects of 10 M and 70 M respectively. Valinomycin (1 nM) antagonized 80 % of the growth-inhibitory effects of 10 M quercetin. The results suggest that at least a part of the antiproliferative effect of quercetin is mediated by a K+ channel blockade. They further confirm a role for K+ channels in mitogenesis and cell proliferation. 相似文献
8.
神经母细胞瘤是儿童期的常见恶性肿瘤之一。临床上,半数以上神经母细胞瘤有明显的N-myc癌基因扩增。神经生长因子(NGF)可使某些神经母细胞瘤细胞分化成神经元样的细胞。但对有N-myc扩增的神经母细胞瘤则可能因NGF受体缺乏而无明显促分化反应。本研究运用重组DNA技术将人NGF受体基因重组到有N-myc扩增,且NGF受体表达很低的神经母细胞瘤系(IMR-32)中,经克隆化培养、筛选,建立了稳定的细胞系—IMR-32/NGFR和对照细胞系IMR-32/NEO。经用抗NGFR的单克隆抗体检测用Flow cytometry技术证实IMR-32/NGFR系中有明显的NGF受体表达,而其母系IMR-32和空病毒对照系IMR-32/NEO则无表达迹象,说明NGF受体表达在IMR-32/NGFR系中是特异的,并能同抗NGFR单克隆抗体特异结合。用Northern B10ting技术亦测得IMR-32/NGFR中NGFR的mRN A明显表达。而其母系IMR-32和对照系IMR-32/NEO则无明显表达。这说明IMR-32/NGFR系中NGFR在mRNA水平上亦是特异的。N-myc和K-ras癌基因在IMR-32、IMR-32/NEO、IMR-32/NGFR三系中无明显变化。在NGF处理后,形态上三系均无明显的分化迹象。但IMR-32/NGFR在神经原纤维轻链的表达上轻度增高。c-fos癌基因的表达见于所有三个细胞系,IMR-32/NGFR略强些。这些说明,在恢复了NGFR基因和表达之后,对N-myc和K-ra 相似文献
9.
Akira Nakagawara Toshimitsu Toyohara Keiichi Ikeda Osami Nada Masazumi Tsuneyoshi 《Virchows Archiv : an international journal of pathology》1986,409(5):571-582
Summary The intratumorous distribution of catecholaminergic clone cells in 23 human neuroblastomas was studied using Falck-Hillarp's method, and the findings compared with the catecholamine (CA) content within the tumour. All the specimens contained elements with CA fluorescence, and the pattern of fluorescence was classified from the distribution of CA-positive cells and neurofibrils, as diffuse cellular (DC); diffuse fibrillary (DF), sporadic (S), clustered (C), island-shaped (I), and bundled (B). The strength of CA fluorescence of both cellular and fibrillary elements correlated well with the CA content within the tumour. In addition, all tumours of urinary VMA-negative cases also contained significantly larger amounts of CA than other, non-functioning, tumours in the paediatric age group. The results of this study suggest that firstly, the ratio of CA-positive cells to CA-positive neuronal processes is proportionately higher in the poorly-differentiated neuroblastomas and that secondly, even tumours negative for urinary VMA or HVA might be polyclonal and contain catecholaminergic elements.This study was supported in part by a Research Grant from the Ministry of Education, Japan (No. 59570549) 相似文献
10.
Targeting of cytokines into the tumor microenvironment using antibody-cytokine fusion proteins, called immunocytokines, represents
a novel approach in cancer immunotherapy. This article summarizes therapeutic efficacy and immune mechanisms involved in targeting
interleukin-2 (IL-2) to neuroectodermal, tumors using ganglioside GD2-specific antibody-IL-2 fusion protein (ch14.18-IL-2).
Treatment of established melanoma metastases with ch14.18-IL-2 resulted in eradication of disease followed by a vaccination
effect protecting mice from lethal challenges, with wild-type tumor calls. In a syngeneic neuroblastoma model, targeted IL-2
was effective in the amplification of a weak memory immune response previously induced by IL-12 gene therapy using an engineered
linear version of this heterodimeric cytokine. These findings show that targeted IL-2 may provide an effective tool in cancer
immunotherapy and establish the missing link between T cell-mediated, vaccination and objective clinical responses. 相似文献