全文获取类型
收费全文 | 2683篇 |
免费 | 214篇 |
国内免费 | 257篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 22篇 |
妇产科学 | 33篇 |
基础医学 | 313篇 |
口腔科学 | 46篇 |
临床医学 | 189篇 |
内科学 | 277篇 |
皮肤病学 | 25篇 |
神经病学 | 239篇 |
特种医学 | 49篇 |
外国民族医学 | 5篇 |
外科学 | 117篇 |
综合类 | 754篇 |
预防医学 | 96篇 |
眼科学 | 47篇 |
药学 | 337篇 |
中国医学 | 328篇 |
肿瘤学 | 268篇 |
出版年
2024年 | 2篇 |
2023年 | 6篇 |
2022年 | 14篇 |
2021年 | 36篇 |
2020年 | 32篇 |
2019年 | 32篇 |
2018年 | 36篇 |
2017年 | 49篇 |
2016年 | 83篇 |
2015年 | 93篇 |
2014年 | 148篇 |
2013年 | 155篇 |
2012年 | 217篇 |
2011年 | 289篇 |
2010年 | 259篇 |
2009年 | 274篇 |
2008年 | 249篇 |
2007年 | 237篇 |
2006年 | 200篇 |
2005年 | 196篇 |
2004年 | 142篇 |
2003年 | 113篇 |
2002年 | 94篇 |
2001年 | 64篇 |
2000年 | 55篇 |
1999年 | 41篇 |
1998年 | 24篇 |
1997年 | 11篇 |
1996年 | 3篇 |
排序方式: 共有3154条查询结果,搜索用时 250 毫秒
991.
Akira Hara Yoshinobu Hirose Naoki Yoshimi Takuji Tanaka Hideki Mori 《Neurological research》2013,35(6):623-628
AbstractExpression of Bcl-2, a programmed cell death (PCD)-suppressing molecule, and Bax, the Bcl-2 related PCDaccelerating protein was investigated in varied human brain tumors. Thirty-six cases ofhuman brain tumors comprising 4 astrocytomas, 3 anaplastic astrocytomas, 4 glioblastomas multiforme, 5 medulloblastomas, 1 ependymoma, 2 choroid plexus papilloma, 1 ganglioglioma, 1 central neurocytoma, 4 meningotheliomatous meningiomas, 3 transitional meningiomas, 4 fibroblastic meningiomas, 3 acoustic neurinomas and. 1 craniopharyngioma were analyzed for the localization of Bax and Bcl-2 proteins. No relationship between the degree of the histological malignancy and the presence of Bax or Bcl-2 proteins was found in varied human brain tumors. However, it is suggested that reduced expression of Bax protein is necessary for the malignant transformation and progression of the brain tumors, since no histologically malignant brain tumors with positive Bax protein were present. Our findings indicate that the expression pattern of Bax and Bcl-2 may reflect histogenetic difference of each type of brain tumors. [Neural Res 1997; 19: 623-628] 相似文献
992.
目的探讨B淋巴细胞瘤-2基因(Bcl-2)和促凋亡基因Bax(Bax)在C57/BL6小鼠海马发育过程中的表达变化。方法取胚龄(E)18、20 d和生后(P)1、3、7、14、21、28 d以及2、3、6、15、18个月的C57/BL6小鼠海马,每组8只,应用免疫组织化学技术及体视学方法检测Bcl-2和Bax蛋白的表达。结果 E18 d~P21 d,在齿状回(DG)的颗粒层、海马阿蒙角(CA)以及CA各区(CA1~CA4)的锥体层,Bcl-2和Bax阳性细胞及其体密度均呈现出先逐渐增加再逐渐降低的趋势,除DG区Bax阳性细胞及其体密度在P14 d达到最高外,其他均在P7 d达到最高(P0.01)。P28 d后均趋于稳定(P0.05)。CA锥体层及DG颗粒层Bcl-2/Bax的体密度比值在P1d显著降低(P0.01),之后趋于稳定(P0.05)。结论小鼠海马Bcl-2和Bax的表达在胚胎发育晚期和生后发育早期较多,而在成年及老年期的表达稳定在较低水平,它们可能参与了海马的塑形过程。 相似文献
993.
目的①在齿科合金浸提液中培养L929细胞检测细胞凋亡相关基因Bcl-2的表达情况;②利用免疫组化的方法从蛋白水平研究生物材料对机体的影响。方法分别提取无镍奥氏体不锈钢、317L不锈钢、金合金的浸提液为L929细胞接种培养,并分别检测在接种后48、72、96 h Bcl-2、Bax表达的程度。结果各实验组在上述时间点,各组细胞的凋亡情况差异有显著性(P<0.01)。Bcl-2的荧光表达程度由强到弱:阴性对照组>金合金组>BIOSSN4含氮无镍奥氏体不锈钢组>317L不锈钢组;Bax的表达强度由强到弱:317L不锈钢组>BIOSSN4含氮无镍奥氏体不锈钢组>金合金组>阴性对照组。结论不同齿科合金的浸提液引起的L929细胞的凋亡程度不同。金合金的生物相容性最好,BIOSSN4含氮无镍奥氏体不锈钢次之,317L不锈钢最差。 相似文献
994.
结直肠癌恶性程度较高,易发生血行、淋巴转移和肝转移。结直肠癌的发生和发展与凋亡密切相关。Bax是Bcl-2家族的重要的促凋亡蛋白,可启动细胞凋亡过程诱导肿瘤细胞发生凋亡。研究表明,Bax的表达预示着结直肠癌的良性预后,而且多数研究认为Bax在结直肠癌中存在高表达。但是Bax是否增强结直肠癌对化疗药物的敏感性,还存有争议。本文就最近的相关文献研究作一综述。 相似文献
995.
Wenjuan Xu Linlin Jing Quanshi Wang Chung-Chih Lin Xiaoting Chen Jianxin Diao Yuanliang Liu Xuegang Sun 《Oncotarget》2015,6(30):30017-30034
Intrinsic apoptosis eliminates cells with damaged DNA and cells with dysregulated expression of oncogene. PGAM5, a member of the phosphoglycerate mutase family, has two splicing variants: PGAM5L (the long form) and PGAM5S (the short form). It has been well established that PGAM5 is at the convergent point of multiple necrosis pathways. However, the role of PGAM5 in intrinsic apoptosis is still controversial. Here we report that the PGAM5L, but not PGAM5S is a prerequisite for the activation of Bax and dephosphorylation of Drp1 in arenobufagin and staurosporine induced intrinsic apoptosis. Knockdown of PGAM5L inhibits the translocation of Bax to the mitochondria and reduces mitochondrial fission. The interaction between PGAM5L and Drp1 was observed in both arenobufagin and staurosporine treated HCT116 cells, but not in HCT116 Bax−/− cells. Bax transfection rescues the formation of the triplex in both arenobufagin and staurosporine stimulated HCT116 Bax−/− cells. Arenobufagin shows remarkable anti-cancer effects both in orthotropic and heterotropic CRC models and demonstrates less toxic effects as compared with that of cisplatin. Bax-PGAM5L-Drp1 complex is detected in arenobufagin and staurosporine treated CRC cells in vitro and in arenobufagin and cisplatin treated tumor in vivo as well. In summary, our results demonstrate that Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution. 相似文献
996.
Ying Zhang Shijing Huang Yanyun Wang Junhua Pan Jun Zheng Xianhui Zhang Yuxia Chen Duojiao Li 《中国神经再生研究》2014,9(1):61-68
The Chinese compound Kaixin fieyu Fang can be used to treat vascular depression; however, the underlying mechanism remains unclear. This study established a rat model of chronic cerebral ischemia-caused white matter damage by ligation of the bilateral common carotid arteries. Rats received daily intragastric administration of a suspension of Kaixin ]ieyu Fang powder. After 3, 7 and 21 days of treatment, the degree of white matter damage in the cerebral ischemia rat model was alleviated, Bcl-2 protein and mRNA expression in brain tissue increased, and Bax protein and mRNA expression decreased. These results indicate that Kaixin Jieyu Fang can alleviate cere- bral white matter damage, and the underlying mechanism is associated with regulation of Bcl-2/ Bax protein and mRNA expression, which is one of possible mechanism behind the protective effect of Kaixin Jieyu Fang against vascular depression. 相似文献
997.
Yaning Zhao Jianmin Li Qiqun Tang Pan Zhang Liwei Jing Changxiang Chen Shuxing Li 《中国神经再生研究》2014,9(7):749-756
Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and KuT0 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and ac- celerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/ reperfusion. 相似文献
998.
目的探讨海马硬化型颞叶癫痫患者海马神经细胞的凋亡及凋亡相关基因的表达。方法癫痫组为15例颞叶癫痫患者手术切除的颞叶病灶,对照组为6例脑外伤内减压术中切除的颞叶脑组织,应用HE染色、原位末端标记(TUNEL)染色及免疫组织化学染色等方法来检测神经细胞凋亡状态及凋亡相关基因bcl-2、bax及半胱氨酸蛋白酶(caspase)-3蛋白的表达。结果对照组及癫痫组HE染色均未发现凋亡的神经细胞;TUNEL染色对照组未见阳性细胞,而癫痫组发现较多的染色阳性细胞,100个染色细胞中阳性细胞数为(4.39±2.04)个。免疫组织化学染色结果表明,对照组患者脑组织内bcl-2蛋白无表达,癫痫组15例均可见bcl-2蛋白表达明显增强[100个染色细胞中阳性细胞数为(6.72±3.36)个],两组比较差异有统计学意义(P〈0.01);bax蛋白在癫痫组与对照组中均轻微表达,两组比较差异无统计学意义(P〉0.05)。对照组有2例检测到caspase-3蛋白的表达,而癫痫组有14例caspase-3蛋白表达明显,100个染色细胞中阳性细胞数分别为(1.07±0.43),(9.54±3.68)个,两组比较差异有统计学意义(P〈0.01)。结论神经细胞凋亡是导致海马硬化的重要原因,bcl-2、caspase-3参与了这一过程并发挥了重要作用。 相似文献
999.
Shahin Asadi Alireza Khabbazi Shahriar Alipour Somayeh Abolhasani Jafar Haji Hossein Amjadi Ebrahim Sakhinia 《International journal of immunogenetics》2020,47(3):309-317
BCL2 and BAX genes are a group of signalling inducer and inhibitor genes playing a key role in the process of cellular physiological death (apoptosis). These genes, through the JAK/STAT signalling pathway, affect different cytokines on cell function and subsequently lead to the pathophysiology of diseases, especially autoimmune diseases. In addition, altering the methylation of genes can affect their expression. Since the aetiology and pathology of Behcet's disease is not fully understood, the aim of this study was to determine the methylation pattern of BCL2 and BAX genes in patients with Behcet's disease and compare it with those of control group. This was a case–control study on 51 patients with Behcet and 61 control subjects. Blood samples were received from all subjects. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method and the methylation of the sites was investigated using quantitative methylation specific PCR (qMS‐PCR) technique after extraction of DNA by salting out method and its examination with Nano drop. The results of methylation and expression of Bax gene suggest that the methylation level in the patient group significantly increased compared to the healthy individuals (p‐value < .05). Furthermore, the results related to Bax gene expression revealed that the mean of gene expression in the patient group has decreased compared to the healthy group, and this decrease was statistically significant (p‐value < .05). The rate of expression and methylation of Bcl2 did not indicate any change in the two patient and healthy groups. Given the results of this study, it can be guessed that perhaps DNA methylation is involved in certain conditions of the disease and it may result in regulation of the expression of the involved genes such as Bax gene, in the pathogenesis of the disease. 相似文献
1000.
目的 探讨广谱半胱天冬氨酸蛋白酶(Caspase)抑制剂z-VAD-fmk对烫伤大鼠肾脏细胞凋亡的影响。方法 48只雄性Wistar大鼠制作严重烫伤模型并随机分为治疗组与对照组各24只。z-VAD-fmk首次剂量3 mg/kg,此后每隔12 h腹腔注射1.5 mg/kg;对照组用等剂量生理盐水干预。两组分别于造模后2、8、24、48 h各处死6只大鼠,取出肾脏。采用TUNEL法检测肾脏细胞凋亡指数(AI),免疫组化法检测B淋巴细胞瘤/白血病-2(bcl-2)和Bcl-2同源拮抗蛋白/致死蛋白(Bax)表达,荧光比色法检测Caspase-3活性。结果 与对照组比较,治疗组造模8、24、48 h AI水平降低、Bax表达水平降低、Bcl-2表达水平升高(P均〈0.05)。两组Caspase-3活性均于伤后8 h达峰值;与对照组比较,治疗组造模2、8、24、48 h Caspase-3活性均降低(P均〈0.05)。结论 z-VAD-fmk可抑制烫伤大鼠早期肾脏细胞的凋亡,其作用机制可能为下调AI、Bcl-2表达水平、Caspase-3活性,上调Bax表达。 相似文献