全文获取类型
收费全文 | 4153篇 |
免费 | 382篇 |
国内免费 | 183篇 |
专业分类
耳鼻咽喉 | 47篇 |
儿科学 | 57篇 |
妇产科学 | 39篇 |
基础医学 | 705篇 |
口腔科学 | 61篇 |
临床医学 | 357篇 |
内科学 | 702篇 |
皮肤病学 | 42篇 |
神经病学 | 759篇 |
特种医学 | 61篇 |
外科学 | 313篇 |
综合类 | 317篇 |
现状与发展 | 3篇 |
预防医学 | 151篇 |
眼科学 | 71篇 |
药学 | 426篇 |
中国医学 | 253篇 |
肿瘤学 | 354篇 |
出版年
2024年 | 11篇 |
2023年 | 102篇 |
2022年 | 125篇 |
2021年 | 268篇 |
2020年 | 201篇 |
2019年 | 184篇 |
2018年 | 158篇 |
2017年 | 145篇 |
2016年 | 197篇 |
2015年 | 199篇 |
2014年 | 276篇 |
2013年 | 310篇 |
2012年 | 216篇 |
2011年 | 246篇 |
2010年 | 173篇 |
2009年 | 167篇 |
2008年 | 185篇 |
2007年 | 150篇 |
2006年 | 144篇 |
2005年 | 125篇 |
2004年 | 91篇 |
2003年 | 94篇 |
2002年 | 52篇 |
2001年 | 56篇 |
2000年 | 38篇 |
1999年 | 54篇 |
1998年 | 56篇 |
1997年 | 46篇 |
1996年 | 39篇 |
1995年 | 46篇 |
1994年 | 46篇 |
1993年 | 38篇 |
1992年 | 36篇 |
1991年 | 30篇 |
1990年 | 34篇 |
1989年 | 33篇 |
1988年 | 37篇 |
1987年 | 24篇 |
1986年 | 22篇 |
1985年 | 44篇 |
1984年 | 61篇 |
1983年 | 36篇 |
1982年 | 45篇 |
1981年 | 18篇 |
1980年 | 14篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 10篇 |
1976年 | 8篇 |
1975年 | 5篇 |
排序方式: 共有4718条查询结果,搜索用时 562 毫秒
1.
《Biomaterials》2015
Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma. 相似文献
2.
胆碱能抗炎通路是一条神经免疫通路,主要依靠乙酰胆碱与巨噬细胞及其他细胞表面上的α7nAchR相结合抑制促炎因子的合成与释放,从而防止组织损伤。α7nAchR是胆碱能递质的主要受体,在胆碱能抗炎通路中起关键作用。针刺治疗有明确的抗炎作用,其作用机制可能与调控α7nAchR激活胆碱能抗炎通路有关。近年来虽然国内外学者对针刺抗炎机制进行了大量研究,然而针刺抗炎的作用机制目前仍不明确。该文从胆碱能抗炎通路概述、α7nAchR结构及功能、α7nAchR的分布、α7nAchR在胆碱能抗炎通路的作用、针刺调控α7nAchR激活胆碱能抗炎通路的机制等方面对针刺调控α7nAchR激活胆碱能抗炎通路进行分析总结,为今后探究针刺抗炎作用机制提供借鉴思路和科学依据。 相似文献
3.
MOB1A regulates glucose deprivation-induced autophagy via IL6-STAT3 pathway in gallbladder carcinoma
Bo Yang Yang Li Rui Zhang Liguo Liu Huijie Miao Yongsheng Li Ziyu Shao Tai Ren Yijian Zhang Qiyu Zhang Yingbin Liu Hongqi Shi 《American journal of cancer research》2020,10(11):3896
MOB kinase activator 1A (MOB1A) plays an important role in many diseases and cancers. Here, we observed that MOB1A was substantially overexpressed in gallbladder carcinoma (GBC) tissues compared with nontumor tissues. The high expression of MOB1A was closely associated with poor survival in patients with GBC at advanced TNM stages. Furthermore, our study indicated that MOB1A promoted autophagy by activating the IL6/STAT3 signaling pathway and regulating the chemosensitivity to gemcitabine under glucose deprivation conditions both in vitro and in vivo. In conclusion, these findings suggested that MOB1A is critical for the development of GBC via the MOB1A-IL6/STAT3-autophagy axis. 相似文献
4.
5.
J. Epelbaum L. Tapia Arancibia J.P. Herman C. Kordon M. Palkovits 《Brain research》1981,230(1-2):412-416
Somatostatin (SRIF) in the central nervous system is mostly concentrated in the median eminence (ME). Immunocytochemical methods have revealed high densities of SRIF-positive perikarya between the preoptic area and the periventricular nucleus of the hypothalamus (NPE). The aim of the present study was to define more precisely the specific pathways of SRIF neurons from NPE to the ME. SRIF levels were measured by radioimmunoassay, following various hypothalamic transections. Frontal periventricular sections decreased SRIF-ME content by 70% (P less than 0.01), when located at the anterior end of the ME but no diminution was observed when the cuts were located anteriorly or posteriorly. Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly. Taken together, our data indicate that most SRIF-containing neurons, originating in the NPE, do not reach the ME directly along the border of the 3rd ventricle; instead they form a loop across the medial forebrain bundle before re-entering the mediobasal hypothalamus at the ME level. 相似文献
6.
Somatosensory nuclei in the brainstem of the rat: independent projections to the thalamus and cerebellum 总被引:2,自引:0,他引:2
The dorsal column nuclei and the sensory trigeminal nuclei project not only to the ventrobasal thalamus but also to the cerebellum. In this study the numbers and distribution of neurones projecting to these two regions were examined for the following nuclei: the rostral part of the main cuneate nucleus, the external cuneate nucleus, nucleus x, the principal sensory nucleus of the trigeminal nerve, and the oral, interpolar, and caudal subnuclei of the spinal nucleus of the trigeminal nerve. A thalamic projection from nucleus x and from the external cuneate nucleus was confirmed, and a distinct group of neurones projecting to the ventroposteromedial thalamus was distinguished near the ventromedial aspect of the principal sensory nucleus. Of the 165,000 neurones examined, only one was found to be double labelled. It was concluded that the populations of neurones that project to the ventrobasal thalamus and to the cerebellum are separate, and that somatosensory neurones in the brainstem do not send axon collaterals to both regions. 相似文献
7.
17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响 总被引:2,自引:0,他引:2
目的研究17β-雌二醇(17β-E2)对子宫内膜异位症(内异症)患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响,探讨Wnt/β-catenin信号通路在介导雌激素促进内异症发生发展的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用不同浓度17β-E2处理子宫内膜间质细胞48 h;此后选用10-10mol/L 17β-E2处理子宫内膜间质细胞12、24和48 h,逆转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测17β-E2处理前后子宫内膜间质细胞β-catenin mRNA和蛋白的表达水平。同法分析雌激素受体拮抗剂ICI182,780(10-6mol/L)对17β-E2促进β-catenin mRNA和蛋白表达的影响。免疫组织化学染色观察17β-E2作用后β-catenin在子宫内膜间质细胞中的定位。结果17β-E2能明显促进内异症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白的表达,并呈剂量和时间依赖性,于10-10mol/L作用48 h最明显。雌激素受体拮抗剂ICI182,780能明显抑制17β-E2对子宫内膜间质细胞β-catenin mRNA和蛋白的表达。免疫组织化学染色发现17β-E2能促进β-catenin在子宫内膜间质细胞核内的表达。结论雌激素可能通过激活Wnt/β-catenin信号通路促进内异症在位子宫内膜的异位种植。 相似文献
8.
细胞内钙信号的变化调节血管平滑肌细胞增殖 总被引:4,自引:0,他引:4
目的探讨细胞内钙信号的变化对大鼠血管平滑肌细胞(VSMC)增殖作用的影响及其对细胞内信号转导机制的变化。方法以培养的大鼠VSMC为模型,用雷尼丁(RY)剌激VSMC内贮Ca2 释放入胞浆,用3H亮氨酸及3H胸腺嘧啶掺入量作为反应VSMC增殖的指标,加入不同的细胞内信号转导阻断剂,观察对RY效应的影响。结果与对照组相比,RY浓度依赖性地促进细胞内游离钙浓度的增高,差异显著(P<0.05或0.01)。RY剌激组蛋白核酸合成速率明显增高,与对照组相比差异显著(P<0.01);尼卡地平(Nicardipine),蛋白激酶C抑制剂(H7),钙调素激酶(CaMPK)抑制剂(W7)和丝裂素活化蛋白激酶(MAPK)抑制剂(PD98059)能明显抑制RY介导的VSMC蛋白核酸合成速率增高,与RY剌激组相比差异显著(P<0.01)。结论细胞内钙信号的变化明显促进VSMC增殖,但其效应可能通过Ca2 、PKC、MAPK来介导。钙离子拮抗剂可抑制血管平滑肌细胞增殖。 相似文献
9.
Voltage-Gated calcium channels and nonvoltage-gated calcium uptake pathways in the rat incisor odontoblast plasma membrane 总被引:4,自引:1,他引:3
Odontoblasts participate actively in the transport and accumulation of Ca2+ ions to the mineralization front during dentinogenesis. These cells are known to carry membrane-bound ATP-driven pumps and
Na+/Ca2+ antiports for Ca2+ extrusion, but little is known about Ca2+ influx mechanisms into these cells. It has been shown that the administration of Ca2+ channel blockers in vivo strongly impairs Ca2+ uptake in the mineral phase during dentinogenesis in the rat; the present in vitro study is aimed at further elucidating
odontoblast Ca2+ uptake mechanisms. Dissected rat incisor odontoblasts exhibited a pronounced fluorescence when incubated with a fluorescently-labeled
(STBodipy) dihydropyridine, which is specific for voltage-gated Ca2+ channels of the L-type, and this binding was competitively abolished by nifedipine. As assayed by fluorescence spectrometry,
odontoblast Ca2+ uptake was enhanced by the agonistic dihydropyridine BAYK-8644 (5 μM) as well as by plasma membrane depolarization in a high
K+ (120 mM) medium. The Ca2+ uptake after depolarization was impaired by nifedipine (5 μM). When treated with the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA; 10 μM), a nonvoltage-gated uptake of 45Ca2+ was identified. This uptake was not influenced by nifedipine (20 μM) but was impaired by lanthanum ions (200 μM). A nonvoltage-gated
uptake of Mn2+ into CPA-treated cells could be traced using the fura-2 quenching technique. This CPA-induced Ca2+ flux was not caused by an alteration of the plasma membrane potential, as assayed with di-8-ANEPPS. The results demonstrate
that Ca2+ flux into dentinogenically active odontoblasts occurs through voltage-gated Ca2+ channels of the L-type and by nonvoltage-gated, agonist-sensitive Ca2+ uptake pathways.
Received: 6 November 1995 / Accepted: 21 February 1996 相似文献
10.
Adrian JonesBN RMN RN PhD student & NormanBA MSC PHD RMN Senior Lecturer 《Journal of psychiatric and mental health nursing》1998,5(1):21-31
Case management has become an established organizational approach to mental health care. However, a recent development of case management, known as 'managed care' has received only limited attention in the UK and this has been confined to acute medical or surgical hospital care. The potential of managed care as applied to mental health care is uncertain. This paper clarifies the nature of managed care and discusses its relevance to mental health care, in particular to the care of people suffering from schizophrenia. The high incidence and heavy resource demands of this user group makes these people an ideal focus for managed care. However, there are conceptual and practical problems hindering its development and implementation, including: the variability and unpredictability of the disease process of schizophrenia; challenges of outcome measurement; and problems relating to the current organization of mental health care. 相似文献