全文获取类型
收费全文 | 994篇 |
免费 | 85篇 |
国内免费 | 200篇 |
出版年
2024年 | 6篇 |
2023年 | 5篇 |
2022年 | 13篇 |
2021年 | 27篇 |
2020年 | 17篇 |
2019年 | 21篇 |
2018年 | 24篇 |
2017年 | 17篇 |
2016年 | 25篇 |
2015年 | 38篇 |
2014年 | 38篇 |
2013年 | 49篇 |
2012年 | 75篇 |
2011年 | 62篇 |
2010年 | 56篇 |
2009年 | 47篇 |
2008年 | 64篇 |
2007年 | 63篇 |
2006年 | 47篇 |
2005年 | 54篇 |
2004年 | 44篇 |
2003年 | 48篇 |
2002年 | 50篇 |
2001年 | 46篇 |
2000年 | 40篇 |
1999年 | 27篇 |
1998年 | 21篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 9篇 |
1994年 | 18篇 |
1993年 | 16篇 |
1992年 | 18篇 |
1991年 | 20篇 |
1990年 | 17篇 |
1989年 | 18篇 |
1988年 | 14篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 8篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1979年 | 5篇 |
1977年 | 3篇 |
1976年 | 6篇 |
1970年 | 5篇 |
1967年 | 6篇 |
1956年 | 3篇 |
排序方式: 共有1279条查询结果,搜索用时 15 毫秒
41.
Toshiaki Nakano Rikiya Kamei Takashi Fujimura Yuki Takaoka Ayane Hori Chia-Yun Lai Kuei-Chen Chiang Yayoi Shimada Naoya Ohmori Takeshi Goto Kazuhisa Ono Chao-Long Chen Shigeru Goto Seiji Kawamoto 《PloS one》2016,11(4)
Nuclear antigens are known to trigger off innate and adaptive immune responses. Recent studies have found that the complex of nucleic acids and core histones that are derived from damaged cells may regulate allergic responses. However, no fundamental study has been performed concerning the role of linker histone H1 in mast cell-mediated type I hyperreactivity. In this study, we explored the impact of histone H1 on mast cell-mediated allergic responses both in vitro and in vivo. In the course of a bona-fide experimental allergen sensitization model upon co-injection with alum adjuvant, ovalbumin (OVA), but not PBS, induced elevated levels of circulating histone H1. Intranasal challenge with histone H1 to OVA/alum- (but not PBS/alum)-sensitized mice induced significantly severer symptoms of allergic rhinitis than those in mice sensitized and challenged with OVA. A monoclonal antibody against histone H1 not only suppressed mast cell degranulation, but also ameliorated OVA-induced nasal hyperreactivity and IgE-mediated passive cutaneous anaphylaxis. Our present data suggest that nuclear histone H1 represents an alarmin-like endogenous mediator acting on mast cells, and that its blockage has a therapeutic potential for mast cell-mediated type I hyperreactivity. 相似文献
42.
Yong Wu Fan-Yan Wei Layla Kawarada Takeo Suzuki Kimi Araki Yoshihiro Komohara Atsushi Fujimura Taku Kaitsuka Motohiro Takeya Yuichi Oike Tsutomu Suzuki Kazuhito Tomizawa 《PLoS genetics》2016,12(9)
Reversible infantile liver failure (RILF) is a unique heritable liver disease characterized by acute liver failure followed by spontaneous recovery at an early stage of life. Genetic mutations in MTU1 have been identified in RILF patients. MTU1 is a mitochondrial enzyme that catalyzes the 2-thiolation of 5-taurinomethyl-2-thiouridine (τm5s2U) found in the anticodon of a subset of mitochondrial tRNAs (mt-tRNAs). Although the genetic basis of RILF is clear, the molecular mechanism that drives the pathogenesis remains elusive. We here generated liver-specific knockout of Mtu1 (Mtu1LKO) mice, which exhibited symptoms of liver injury characterized by hepatic inflammation and elevated levels of plasma lactate and AST. Mechanistically, Mtu1 deficiency resulted in a loss of 2-thiolation in mt-tRNAs, which led to a marked impairment of mitochondrial translation. Consequently, Mtu1LKO mice exhibited severe disruption of mitochondrial membrane integrity and a broad decrease in respiratory complex activities in the hepatocytes. Interestingly, mitochondrial dysfunction induced signaling pathways related to mitochondrial proliferation and the suppression of oxidative stress. The present study demonstrates that Mtu1-dependent 2-thiolation of mt-tRNA is indispensable for mitochondrial translation and that Mtu1 deficiency is a primary cause of RILF. In addition, Mtu1 deficiency is associated with multiple cytoprotective pathways that might prevent catastrophic liver failure and assist in the recovery from liver injury. 相似文献
43.
EMS对三个玉米自交系的诱变效应分析 总被引:1,自引:0,他引:1
EMS诱变玉米花粉是玉米化学诱变的主要技术。该研究以生产上3个常用的玉米自交系K305、21-ES、R08为材料,对其花粉用不同浓度的EMS诱变处理,探讨其EMS诱变的最佳浓度范围,明确其诱变效应。结果表明:3个自交系经过不同浓度的EMS诱变后,其结实率随着浓度的增大表现出减小的趋势,从其半致死剂量来看,EMS诱变花粉的适宜浓度范围自交系K305和R08均为0.67~1.0 mL?L-1,21-ES在1.67 mL?L-1附近。 M1代不同性状其变异幅度和变异系数与对照相比主要表现出增大的趋势,其不同性状的生物学效应在材料间表现不一致,表明性状在不同材料间对EMS的敏感性不一样,生育期表现为21-ES>K305>R08;主要株型性状表现为R08>21-ES>K305;主要雄穗性状K305和21-ES比R08敏感;主要果穗性状表现为21-ES>K305>R08。 M2代整体表现为变异谱扩大,其株高、穗位高和叶面积以及主要果穗性状的变异表现复杂,主要雄穗性状中除K305的M2株系雄穗分枝数呈双向变异外,其余M2株系整体偏向于雄穗变短,雄穗分枝数减小。该研究结果为后续研究和应用打下了基础。 相似文献
44.
Efficient modification of the myostatin gene in porcine somatic cells and generation of knockout piglets
下载免费PDF全文
![点击此处可从《Molecular reproduction and development》网站下载免费的PDF全文](/ch/ext_images/free.gif)
45.
目的:探讨经皮穴位电刺激(TEAS)对老年髋关节置换术患者脑氧代谢以及术后认知功能、镇痛效果的影响。方法:选取2016年1月~2018年7月期间我院收治的行髋关节置换术患者91例为研究对象,将研究对象根据随机数字表法分为对照组(n=45)和研究组(n=46),对照组给予常规麻醉处理,研究组在对照组基础上给予TEAS,比较两组脑氧代谢、术后认知功能以及镇痛效果,记录两组术后的不良反应发生情况。结果:在降压开始后20 min(T1)、降压开始后40 min(T2)、停止降压后20 min(T3)时间点时,两组静脉血氧含量(Cjv O2)较降压前即刻(T0)时间点升高,且研究组高于对照组(P0.05),两组脑动-静脉血氧含量差(Da-jvO2)、脑氧摄取率(CERO2)较T0时间点降低,且研究组低于对照组(P0.05)。两组患者术后72h简易智能量表(MMSE)评分均较术前24h降低,但研究组高于对照组(P0.05),研究组术后认知功能障碍(POCD)发生率低于对照组(P0.05)。与术前比较,两组患者术后8h、术后24h、术后48h视觉疼痛模拟量表(VAS)评分均升高(P0.05),但研究组术后8h、术后24h、术后48h等时间点VAS评分均低于对照组(P0.05)。两组患者不良反应总发生率比较无差异(P0.05)。结论:TEAS对老年髋关节置换术后患者的镇痛效果确切,可有效改善脑氧代谢情况,提高术后认知功能,临床应用价值较高。 相似文献
46.
目的:探讨杨芽黄素对前列腺癌细胞22Rv.1的作用及机制。方法:将0~20μg/ml杨芽黄素作用于22Rv.1细胞和正常前列腺细胞RWPE-1,适时采用MTS法检测细胞的增殖活性,采用流式细胞仪、hoechst染色、LDH释放实验分别检测22Rv.1细胞凋亡、死亡、周期、核型变化和药物的细胞毒作用,利用qPCR和Westernblot分析22Rv.1细胞内基因转录和蛋白表达的改变,并通过抑瘤实验证实该药的抑癌作用。结果:杨芽黄素可显著抑制22Rv.1细胞增殖、诱导其凋亡,促进22Rv.1细胞凋亡相关基因dr4、dr5、trail、p53、caspase-3、caspase-8、caspase-9、bid、bax、foxo3的表达,并抑制抗凋亡基因akt、pi3k和bcl-2的表达。结论:杨芽黄素可通过影响TRAIL和PI3K/AKT信号通路诱导前列腺癌细胞凋亡,具有抗前列腺癌的作用。 相似文献
47.
不同种植年限猕猴桃园土壤微生物功能多样性研究 总被引:2,自引:0,他引:2
陕西秦岭北麓是世界上最大的猕猴桃生产基地,长期相对单一的果树种植方式导致不同种植年限果园土壤微生态环境差异。研究猕猴桃园土壤微生物功能多样性随种植年限的变化特征,为果园土壤科学管理提供参考。采集不同种植年限猕猴桃根际土壤,应用平板菌落计数法和Biolog-Eco法研究土壤微生物的数量、种群以及功能多样性,并对土壤微生物功能多样性与土壤养分的相关性进行分析。结果显示,猕猴桃园土壤可培养微生物以细菌为主,其次是放线菌,真菌数量最少。随着种植年限的增加,细菌和放线菌数量显著降低,而真菌数量显著升高。微生物平均颜色变化率(average well-color development,AWCD)、微生物群落Shannon-Wiener指数(H′)、Simpson指数(D)及McIntosh指数(U)均随种植年限的增加而显著降低。主成分分析显示,不同种植年限猕猴桃园土壤微生物碳源利用特征明显不同,0~5 a、5~10 a和10~20 a的猕猴桃园土壤微生物群落分别被划分在载荷图的第一、第四和第三象限。猕猴桃园土壤微生物对糖类、氨基酸类和酯类的利用率相对较高,而对醇类、胺类和酸类的利用率相对较低。对第1主成分贡献大的碳源(|r|≥0.5)有11种,其中糖类占36%,氨基酸类和酯类均占18%。土壤微生物功能多样性与土壤养分相关性分析表明,土壤微生物功能多样性与土壤有机质正相关,与有效磷和速效钾负相关。结果表明,随种植年限的增加,猕猴桃园土壤微生物的数量和结构发生变化,微生物功能多样性降低,对碳源利用能力降低。鉴于土壤微生物功能多样性与土壤养分的相关性,应合理加大有机肥施用量,适量减少有效磷和速效钾的施用量。 相似文献
48.
49.
50.
Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloproteinase with two disintegrin-like sequences 总被引:8,自引:0,他引:8
Ito M Hamako J Sakurai Y Matsumoto M Fujimura Y Suzuki M Hashimoto K Titani K Matsui T 《Biochemistry》2001,40(14):4503-4511
The primary structure of kaouthiagin, a metalloproteinase from the venom of the cobra snake Naja kaouthia which specifically cleaves human von Willebrand factor (VWF), was determined by amino acid sequencing. Kaouthiagin is composed of 401 amino acid residues and one Asn-linked sugar chain. The sequence is highly similar to those of high-molecular mass snake venom metalloproteinases from viperid and crotalid venoms comprised of metalloproteinase, disintegrin-like, and Cys-rich domains. The metalloproteinase domain had a zinc-binding motif (HEXXHXXGXXH), which is highly conserved in the metzincin family. Kaouthiagin had an HDCD sequence in the disintegrin-like domain and uniquely had an RGD sequence in the Cys-rich domain. Metalloproteinase-inactivated kaouthiagin had no effect on VWF-induced platelet aggregation but still had an inhibitory effect on the collagen-induced platelet aggregation with an IC(50) of 0.2 microM, suggesting the presence of disintegrin-like activity in kaouthiagin. To examine the effects of these HDCD and RGD sequences, we prepared synthetic peptides cyclized by an S-S linkage. Both the synthetic cyclized peptides from the disintegrin-like domain and from the Cys-rich domain) had an inhibitory effect on collagen-induced platelet aggregation with IC(50) values of approximately 90 and approximately 4.5 microM, respectively. The linear peptide (RAAKHDCDLPELC) and the cyclized peptide had little effect on collagen-induced platelet aggregation. These results suggest that kaouthiagin not only inhibits VWF-induced platelet aggregation by cleaving VWF but also disturbs the agonist-induced platelet aggregation by both the disintegrin-like domain and the RGD sequence in the Cys-rich domain. Furthermore, our results imply that the corresponding part of the Cys-rich domain in other snake venom metalloproteinases also has a synergistic disturbing effect on platelet aggregation, serving as a second disintegrin-like domain. This is the first report of an elapid venom metalloproteinase with two disintegrin-like sequences. 相似文献