全文获取类型
收费全文 | 131738篇 |
免费 | 14120篇 |
国内免费 | 4377篇 |
专业分类
耳鼻咽喉 | 874篇 |
儿科学 | 2052篇 |
妇产科学 | 1481篇 |
基础医学 | 24172篇 |
口腔科学 | 3278篇 |
临床医学 | 9314篇 |
内科学 | 19979篇 |
皮肤病学 | 2264篇 |
神经病学 | 13937篇 |
特种医学 | 3217篇 |
外国民族医学 | 35篇 |
外科学 | 10213篇 |
综合类 | 13806篇 |
现状与发展 | 17篇 |
预防医学 | 5342篇 |
眼科学 | 1527篇 |
药学 | 20528篇 |
54篇 | |
中国医学 | 5720篇 |
肿瘤学 | 12425篇 |
出版年
2024年 | 317篇 |
2023年 | 2445篇 |
2022年 | 3829篇 |
2021年 | 6505篇 |
2020年 | 5497篇 |
2019年 | 5635篇 |
2018年 | 5449篇 |
2017年 | 5297篇 |
2016年 | 5127篇 |
2015年 | 5762篇 |
2014年 | 8315篇 |
2013年 | 8682篇 |
2012年 | 7631篇 |
2011年 | 8761篇 |
2010年 | 6920篇 |
2009年 | 6890篇 |
2008年 | 6809篇 |
2007年 | 5806篇 |
2006年 | 4929篇 |
2005年 | 4506篇 |
2004年 | 3811篇 |
2003年 | 3401篇 |
2002年 | 2555篇 |
2001年 | 2183篇 |
2000年 | 1801篇 |
1999年 | 1721篇 |
1998年 | 1610篇 |
1997年 | 1548篇 |
1996年 | 1410篇 |
1995年 | 1252篇 |
1994年 | 1161篇 |
1993年 | 1107篇 |
1992年 | 884篇 |
1991年 | 795篇 |
1990年 | 675篇 |
1989年 | 581篇 |
1988年 | 555篇 |
1987年 | 553篇 |
1986年 | 661篇 |
1985年 | 992篇 |
1984年 | 1037篇 |
1983年 | 797篇 |
1982年 | 774篇 |
1981年 | 669篇 |
1980年 | 593篇 |
1979年 | 493篇 |
1978年 | 336篇 |
1977年 | 262篇 |
1976年 | 299篇 |
1975年 | 195篇 |
排序方式: 共有10000条查询结果,搜索用时 336 毫秒
951.
The pro-inflammatory cytokine interleukin-1β (IL-1β) is released by cells during injury and stress, and increased neuronal expression of IL-1β is a feature of age-related neurodegeneration. We have recently reported that IL-1β has a biphasic effect on the K+-induced rise in intracellular Ca2+ concentration ([Ca2+]i) in cortical synaptosomes, exerting an inhibitory effect on the K+-induced rise in [Ca2+]i at lower (3.5 ng/mL) concentrations and a stimulatory effect on the K+-induced rise in [Ca2+]i at higher (100 ng/mL) concentrations. In the present study, we observed that the K+-induced rise in [Ca2+]i was inhibited to a similar extent by the lower concentration of IL-1β in cortical synaptosomes prepared from young (3-month-old), middle-aged (12-month-old) and aged (24-month-old) rats. In contrast, cortical synaptosomes prepared from the aged rats exhibited an increased susceptibility to the higher concentration of IL-1β, resulting in a marked elevation in [Ca2+]i. We propose that the age-related increase in neuronal concentration of IL-1β promotes a dramatic elevation in [Ca2+]i following membrane depolarization, thereby altering Ca2+ homeostasis and exacerbating neuronal vulnerability to excitotoxicity. 相似文献
952.
pitx3和nurr1基因在不同年龄大鼠不同脑区的表达变化 总被引:1,自引:0,他引:1
目的:探讨正常不同年龄SD大鼠不同脑区pitx3、nurr1基闪的表达变化.方法:使用RT-PCR、免疫印迹法和免疫荧光方法检测pitx3、nurr1基因在正常不同年龄SD大鼠不同脑区转录与翻译水平的表达.结果:RT-PCR、免疫印迹法检测显示,pitx3、nurr1基因在各年龄组火鼠中脑、大脑皮质、海马、纹状体、嗅球和下丘脑均有表达,其中在海马和中脑表达较高;在各年龄组中新生组表达最高,并随着年龄的增长表达呈下凋趋势;免疫荧光检测E16.5 d组和新生组的中脑和海马区观察到有大量Pitx3或Nurr1单标细胞和Pitx3/TH或Nurrl/TH双标细胞.结论:pitx3、nurr1基凶的表达小仅与中脑多巴胺能神经元,而且可能与儿茶酚胺类神经元的发育和生存维持有关;老年期pitx3、nurr1基因表达下降可能与脑老化和神经退行性变疾病.如帕金森病和老年性痴呆等有关. 相似文献
953.
目的 研究食管癌细胞Eca-109增殖、凋亡及COX-2表达与信号转导子和激活子3(STAT3)信号传导通路的关系,明确以JAK2/STAT3为靶向的信号转导在Eca-109细胞中的分子调控机制。方法 将JAK2抑制剂AG490作用于Eca-109细胞,用MTT法检测细胞增殖;流式细胞仪、DNA琼脂糖电泳法及透射电子显微镜检测细胞凋亡;Western blot法检测细胞中JAK2、p-JAK2、p-Stat3及COX-2的蛋白表达变化;RT-PCR 检测COX-2 mRNA的变化。结果 AG490呈时间、剂量依赖性的抑制Eca-109细胞增殖并诱导凋亡,抑制JAK2/STAT3通路蛋白的表达,呈浓度依赖性地下调p-JAK2及p-Stat3蛋白的表达(P <0.05),并下调COX-2 mRNA及蛋白的表达(P <0.05)。结论 JAK2/STAT3信号传导通路调控AG490对Eca-109细胞作用的细胞内信号传导机制,最终通过下调COX-2表达影响Eca-109细胞的增殖并诱导凋亡。 相似文献
954.
Andrea M. Gross Megan Frone Karen W. Gripp Bruce D. Gelb Lisa Schoyer Lisa Schill Beth Stronach Leslie G. Biesecker Dominic Esposito Edjay Ralph Hernandez Eric Legius Mignon L. Loh Staci Martin Deborah K. Morrison Katherine A. Rauen Pamela L. Wolters Dina Zand Frank McCormick Sharon A. Savage Douglas R. Stewart Brigitte C. Widemann Marielle E. Yohe 《American journal of medical genetics. Part A》2020,182(4):866-876
RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1‐related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, selumetinib was granted breakthrough therapy designation by the FDA for the treatment of PN. Other RASopathy manifestations may also benefit from RAS targeted therapies. The overall goal of Advancing RAS/RASopathy Therapies (ART), a new NCI initiative, is to develop effective therapies and prevention strategies for the clinical manifestations of the non‐NF1 RASopathies and for tumors characterized by somatic RAS mutations. This report reflects discussions from a February 2019 initiation meeting for this project, which had broad international collaboration from basic and clinical researchers and patient advocates. 相似文献
955.
Kenji Naritomi Yoshinori Izumikawa Noriko Kinjo Chuken Miyagi Kiyotake Hirayama 《Journal of human genetics》1989,34(2):113-121
To identify the origin of a small inserted segment in ade novo 8p+ chromosome, an originally programmed computerized data-base for chromosomal aberration syndromes was utilized. The system selected 3q2 trisomy and 10q2 trisomy as candidates. As a result of a careful comparison of several high-resolution banding patterns among chromosomes 3, 10 and the inserted segment, her karyotype was disignated as: 46,XX,–8,+der(8), inv ins(8;3)(p21.1;q26.32q24)de novo. A small segment from 3q24 to 3q26.32 was trisomic, and invertedly inserted into the short arm of chromosome 8. This computerized database was considered to be useful for analyses of the smallde novo inserted chromosomal segment. 相似文献
956.
Liposomes could bind and fuse efficiently to human erythrocytes in the presence of HVJ when they contained gangliosides isolated from human erythrocytes. Sialosylparagloboside, which has a terminal sequence of NeuAcα2?3Ga1β1?4GlcNac, has a much higher receptor activity to the virus than GD1a, GD1b, GT1b, and GT1a, all of which contain the terminal sequence of NeuAcα2?3Galβ1?3GalNAc or NeuAcα2?8NeuAcα2?3Galβ1?3GalNAc. The activity of sialosylparagloboside is comparable to that of glycophorin, a major sialoglycoprotein of human erythrocytes, when compared on the basis of the required amount (as sialic acid) of compounds. The high affinity of sialosylparagloboside to the viral HANA protein is also suggested by the finding that it showed high inhibitory activity against HVJ-mediated binding of glycophorin liposomes to erythrocytes. Sialosylparagloboside was also highly susceptible to the viral sialidase, the other biological function of HANA protein. 相似文献
957.
Eiji Tanaka Kendo Kiyosawa Yoshiyuki Nakatsuji Yoshimichi Inoue Tatsuo Miyamura Joe Chiba Seiichi Furuta 《Journal of medical virology》1993,39(4):318-324
The prevalence of hepatitis C antibodies (anti- HCV) among multitransfused patients was studied and compared with predicted values obtained from a post-transfusion hepatitis study and from data on the prevalence of anti-HCV among blood donors. The prevalence of hepatitis B core antibodies (anti-HBc) was also studied to determine the routes of transmission of hepatitis C virus. The patients consisted of 65 dialysis patients (57 on haemodialysis and 8 on continuous ambulatory peritoneal dialysis) and 71 leukemia patients in long-term remission [49 with acute myeloid leukemia (AML) and 22 with acute lymphatic leukemia (ALL)]. The presence of anti-HCV was investigated using a second generation enzyme-linked immunosorbent assay. Reactive samples were confirmed by a second generation recombinant immunoblot assay. Anti-HBc was studied in the 65 dialysis patients and in 40 of the leukemia patients. Three (4.6%) of the 65 dialysis patients and 12 (24.5%) of the 49 AML patients were anti-HCV positive whereas all of the ALL patients were seronegative. The total number of blood units transfused to 134 patients (data on two dialysis patients were not available) was 18,148, out of which 17,575 units had been transfused prior to the initiation of anti- HCV screening of blood donors. On the basis of the anti-HCV prevalence among blood donors and the incidence of post-transfusion hepatitis, the predicted number of seropositive patients was 11 and 18, respectively. Five of the 65 dialysis patients were anti-HBc positive, compared with only one of the 40 leukemia patients. It is concluded that the anti-HCV prevalence among dialysis and leukemia patients is concordant with the risk of receiving contaminated blood products, whereas hepatitis B infection may have other routes of transmission in dialysis patients. © 1993 Wiley-Liss, Inc. 相似文献
958.
Effects of ruthenium red on membrane ionic currents in urinary bladder smooth muscle cells of the guinea-pig 总被引:2,自引:0,他引:2
Masaru Hirano Y. Imaizumi Katsuhiko Muraki A. Yamada Minoru Watanabe 《Pflügers Archiv : European journal of physiology》1998,435(5):645-653
Three major ionic currents, Ca2+-dependent K+ current (I
K-Ca), delayed rectifier type K+ current (I
kd) and Ca2+ current (I
Ca), were activated by depolarization under whole-cell clamp in single smooth muscle cells isolated from guinea-pig urinary
bladder. Externally applied ruthenium red (RuR) reduced the amplitude of I
K-Ca and I
Ca at 0 mV (IC50 values were 4.2 and 5.6 μM, respectively), but did not affect I
Kd. Spontaneous transient outward currents (STOCs) and caffeine-induced outward currents (I
caf) at –30 mV were reduced by external 10 μM RuR. When 10 μM RuR was added to the pipette solution, I
K-Ca during depolarization, STOCs and I
caf significantly decreased with time. RuR did not change the unitary current amplitude of the large-conductance Ca2+-dependent K+ (BK) channels, but reduced the open probability of the channel under excised patch-clamp recording mode. RuR reduced the
channel activity more effectively from the cytosolic face than from the other. This inhibition decreased when the cytosolic
Ca2+ concentration was increased. These results indicate that RuR blocks BK and Ca2+ channels in urinary bladder smooth muscle cells. The decrease in I
K-Ca, STOCs and I
caf by RuR is attributable to the direct inhibition of BK channel activity, probably in addition to the inhibition of Ca2+ release from storage sites. The direct inhibition of BK channel activity by RuR may be related to the interaction of RuR
with the Ca2+-binding sites of the channel protein.
Received: 15 October 1997 / Received after revision and accepted: 25 November 1997 相似文献
959.
Haruyo Nakajima PhDa Satoshi Hachimuraa Shinya Nishiwakia Toshiyuki Katsuki MD PhDb Naoki Shimojo MD PhDb Akio Ametani PhDa Yoichi Kohno MD PhDb Shuichi Kaminogawa PhDa 《The Journal of allergy and clinical immunology》1996,97(6):1342-1349
To study cow’s milk allergy at the cellular level, we assessed the reactivity of peripheral blood mononuclear cells from patients allergic to cow’s milk to αs1-casein, which is one of the major allergens in cow’s milk. Proliferation of the cells to αs1-casein activation showed a rather weak response. Therefore to understand T-cell reactivity to αs1-casein in more detail, we prepared αs1-casein–specific T-cell lines from patients allergic to cow’s milk and established 26 T-cell lines. These T-cell lines could be classified into three groups by analyzing their surface marker expression: those containing predominantly CD4+CD8- T cells, those containing both CD4+CD8- and CD4-CD8+ T cells, and those containing predominantly CD4-CD8+ T cells. The CD8+ T cells were obtained at an unexpectedly higher frequency from the patients. These T-cell lines produced interferon-γ and IL-4. These results suggest that CD8+ T cells specific for αs1-casein and CD4+ T cells were primed by the stimulation with αs1-casein in patients allergic to milk and that both T cells may play a key role in the onset, progression of, or recovery from cow’s milk allergy. (J ALLERGY CLIN IMMUNOL 1996;97:1342-9.) 相似文献
960.
淋巴细胞经TCR-CD3活化增殖作用的分析 总被引:1,自引:0,他引:1
本文探讨了抗CD3单抗诱导的淋巴细胞活化增殖及有关影响因素。实验结果表明:①淋巴细胞内钙升高是淋巴细胞活化增殖的重要条件,CD3McAb引起的早期胞浆游离钙迅速升高主要由内质网释放钙离子所致,而淋巴细胞增殖不仅需要细胞内钙释放,还需要细胞外钙内流;②GTP结合蛋白是淋巴细胞激活过程的一重要环节,经G蛋白作用物霍乱毒素作用后,淋巴细胞DNA合成显著降低;③新霉素和PSS可抑制PLC和PkC的活性,对淋巴细胞NDA合成造成剂量依赖性抑制作用。此外,抗CD3McAb诱导的淋巴细胞DNA合成需要辅佐细胞的存在,高度纯化的T细胞对CD3McAb的刺激不发生增殖反应。 相似文献