首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   15617篇
  免费   1701篇
  国内免费   3480篇
  2024年   23篇
  2023年   331篇
  2022年   434篇
  2021年   829篇
  2020年   643篇
  2019年   851篇
  2018年   730篇
  2017年   622篇
  2016年   749篇
  2015年   1029篇
  2014年   1277篇
  2013年   1304篇
  2012年   1569篇
  2011年   1449篇
  2010年   988篇
  2009年   918篇
  2008年   1051篇
  2007年   954篇
  2006年   886篇
  2005年   733篇
  2004年   624篇
  2003年   534篇
  2002年   474篇
  2001年   328篇
  2000年   271篇
  1999年   204篇
  1998年   153篇
  1997年   120篇
  1996年   95篇
  1995年   55篇
  1994年   60篇
  1993年   42篇
  1992年   63篇
  1991年   51篇
  1990年   54篇
  1989年   41篇
  1988年   21篇
  1987年   22篇
  1986年   36篇
  1985年   24篇
  1984年   23篇
  1983年   27篇
  1982年   17篇
  1981年   13篇
  1980年   7篇
  1979年   17篇
  1978年   7篇
  1977年   10篇
  1976年   9篇
  1975年   7篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
31.
Three major forms of monoiodinated VIP (M125I-VIP) were isolated after chloramine-T iodination and HPLC purification. The iodinated tyrosine residue was located in each form of M125I-VIP using arginase C and trypsin digestion for obtaining defined fragments containing only one tyrosine residue. The HPLC isolated iodinated fragments thus obtained were used for HPLC comigration studies with iodinated synthetic C and N terminal VIP fragments and for amino acid analysis. The first two eluting peaks 1 and 2 are (M125I-Tyr10-VIP); peak 1 has an oxidized methionine; peak 3 is a (M125I-Tyr22-VIP) which also has an oxidized methionine. A reduced counterpart of peak 3 named peak 4 was isolated by further HPLC analysis. The ability of the different species of M125I-VIP to stimulate adenosine cyclic 3',5'-phosphate (cAMP) production in transformed colonic cells in culture (HT-29) was compared to that of native VIP. The mean potencies of the M125I-VIP species expressed as a percentage relative to the potency of native VIP were, peak (1): 0.98; (2): 0.84; (3): 1.38; (4): 1.48, in the range of concentrations tested (2-60 pM). The M125I-Tyr22-VIP are significantly more active than native VIP (P less than 0.01). Oxidation of methionine or iodination of tyrosine 10 does not significantly modify the biological activity of VIP. We conclude that iodination of Tyr-22 located in the apolar helical COOH-terminal of VIP increases the effectiveness of VIP interaction with its receptors. Thus the tyrosyl residue and the localized hydrophobic features of VIP are critically involved in the function of this neurotransmitter.  相似文献   
32.
肝细胞癌(hepatocellular carcinoma,HCC)治疗困难、预后很差,是肿瘤相关死亡中的第4大癌症,严重危害人类生命健康,但其具体发病机制却仍未完全阐明。因此,探索能调控肝细胞癌发生发展,作为肝细胞癌的诊断标志物或能预测患者预后的关键分子仍十分必要。环状RNA是前体mRNA通过反向剪接产生的由3′, 5′ 磷酸二酯键首尾连接形成的共价闭合环状结构,主要有外显子circRNA(exonic circRNA,ecircRNA)、环状内含子RNA(circular intronic RNA,ciRNA)及外显子 内含子circRNA(exon-intron circRNA,EIciRNA)三大类。由于环状RNA具有普遍性、高度保守性和稳定性,其可以参与多种癌症的发生发展过程,并且可作为肿瘤的早期诊断标志物及预后因子,因此,这是一类新型且非常有潜力应用于临床诊治各阶段的分子。近年来,有大量关于环状RNA与肝细胞癌的研究。这些研究表明,环状RNA在肝细胞癌发生发展进程中发挥的作用十分重要,并且其机制多样。因此,本文主要关注环状RNA在肝细胞癌中的最新进展,总结不同环状RNA分子对于肝细胞癌细胞恶性表型、肿瘤干细胞及肿瘤微环境中免疫细胞的作用,以及其在肝细胞癌临床转移、分期、诊断、预后等各阶段中发挥的功能及其具体作用机制。此外,本文还提出了目前研究中存在的一些问题和不足,以期为未来的研究提供一些新的思路及策略。  相似文献   
33.
长非编码RNA(long non-coding RNAs, lncRNAs)在肿瘤发生、发展进程中承担重要角色,是近年来的研究热点之一。大量研究表明,浆细胞瘤变异易位基因1(plasmacytoma variant translocation 1, PVT1)可通过多种分子机制参与调控消化系统肿瘤的增殖凋亡、迁移侵袭、细胞自噬、血管生成、多药耐药及肿瘤代谢等过程,从而发挥致癌作用。本文主要就PVT1在消化系统肿瘤中的表达水平变化,及其与临床病理特征和预后的关系,以及PVT1对消化系统肿瘤的致癌作用机制和多药耐药机制等研究进展作一综述。  相似文献   
34.
Apolipoprotein (apo-) E2 and beta-migrating very low density lipoproteins (beta-VLDL) (which were isolated from type III hyperlipoproteinemic subjects) both demonstrated defective binding to apo-E and apo-B,E receptors on dog liver membranes and to apo-B,E low density lipoproteins (LDL) receptors on fibroblasts. The defective binding activity of the apo-E2 and beta-VLDL varied from very poor to nearly normal. The ability of the beta-VLDL to interact with hepatic apo-E receptors was enhanced by the addition of normal apo-E3 to the beta-VLDL. Furthermore, cysteamine treatment of the apo-E2 in beta-VLDL enhanced binding of the beta-VLDL to both apo-E and apo-B,E receptors. The importance of apo-E in mediating the receptor binding of beta-VLDL to these receptors was confirmed by using monoclonal antibodies. The residual binding activity of beta-VLDL to apo-E and apo-B,E receptors was inhibited by greater than 90% with anti-apo-E, while the addition of anti-apo-B had little effect. The apo-B in the beta-VLDL was capable of binding to apo-B,E receptors after the hydrolysis of the beta-VLDL triglycerides with milk lipoprotein lipase. Lipase treatment yielded, two subfractions of beta-VLDL. One fraction (d = 1.02 to 1.03 g/ml) was enriched with apo-B100; the other fraction (d less than 1.006 g/ml) was enriched with apo-B48 and apo-E2. Significantly increased amounts of the apo-B100-enriched fraction bound to apo-B,E receptors. Inhibition of this binding caused by the addition of anti-apo-B indicated that the binding activity of this subfraction was mediated by apo-B100. The apo-B48-enriched fraction did not show a significant increase in receptor binding, suggesting that apo-B48 does not bind to these receptors. In a control experiment, it was shown that triglyceride-rich VLDL, which contain normal apo-E3 and apo-B100, bind significantly to both liver apo-E receptors and fibroblast apo-B,E receptors. This binding activity was inhibited by greater than 90% with anti-apo-E. Lipase hydrolysis of the VLDL did not further enhance their receptor-binding activity. These results demonstrate that apo-E, and not apo-B, is the major determinant mediating the receptor-binding activity of cholesterol-rich beta-VLDL and triglyceride-rich VLDL.  相似文献   
35.
The groin flap in reparative surgery of the hand   总被引:2,自引:0,他引:2  
The historical literature of the use of axial vascular pattern flaps from the hypogastric and iliofemoral regions in reparative surgery of the hand is concisely reviewed. Thirty-six iliofemoral (groin) flaps were utilized for delayed primary resurfacing and secondary reconstruction of defects of the hand and forearm. Two flaps (6 percent) were complicated by partial necrosis. We caution against the immediate resurfacing (within 24 hours of injury) of acute crushed hand wounds by distant flaps. The immediate application of a healthy flap on a soiled or crushed wound invites complications of local tissue necrosis, infection, and subsequent loss of the flap. When distant flaps are indicated for coverage of acute hand wounds, delayed primary coverage following complete removal of all nonviable tissue is a safe and reliable regimen. It is advantageous to design the serviceable portion of the flap on the distal area of the vascular territory of the groin flap. Thoughtful yet "radical" defatting can be performed on the lateral portion of the groin flap territory. Constructed in this way, the long medial base of the groin flap allows freedom for movement at the wrist and metacarpophalangeal and interphalangeal joints, thus decreasing edema and stiffness. In the management of soft-tissue defects in the hand requiring distant flap coverage, we choose to utilize the conventional groin flap in preference to the microvascular free flap when both techniques will deliver equal results.  相似文献   
36.
水蒸汽蒸馏巴柑檬叶和果皮精油化学成分的研究   总被引:1,自引:0,他引:1  
巴柑檬是我们第一次从国外引种成功的一种名贵香料植物。用色谱-质谱-计算机联用技术、毛细管气相色谱保留指数法和标准品叠加法分析了水蒸汽蒸馏巴柑檬叶和果皮精油的化学成分。从叶和果皮精油分离出来的220个和200个成分中,分别鉴定出48个和57个成分。鉴定组分的含量分别占叶和果皮精油的99.80%和98.54%。叶精油与果皮精油在化学成分方面的主要区别是叶油中萜烃化合物含量较低,而萜醇类化合物含量较高。  相似文献   
37.
The polymorphic phase behaviour of dilinoleoylphosphatidyethanolamine (DLPE) and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) is investigated by freeze-fracture electron microscopy, X-ray diffraction and 31P-NMR. The structures at 5% or less POPC are predominantly inverted hexagonal (HII), whereas at 15% or more POPC, the structure is mostly bilayer (L), interrupted by defects (lipidic particles). A cubic phase structure is observed in the transition range between H and L phases; the cubic arrangement deteriorates at higher temperatures into an amorphous aggregate of spherical units. Both cubic and amorphous structures contribute to the isotropic 31P resonance, with no preference for PC or PE partitioning in the isotropic motion as observed by high resolution NMR. The existence of the cubic phase seems to depend critially on the homogeneity and the degree unsaturation of the phospholipids.  相似文献   
38.
金丝猴的牙齿   总被引:6,自引:1,他引:5  
牙齿对古生物、古人类研究是十分重要的。牙齿也是动物分类学所依据的重要特征之一,它所提供的亲缘证据和来自其他方面的材料多是相吻合的。在讨论和评价现生灵长类时,牙齿同样是不可缺少的材料之一。就目前所知,已发表的金丝猴(Rhinopithecus)牙齿的研究资料较少。Hooiier(1952)和Swindler(1976)对川金丝猴的牙齿只作了一个简单的记录和扼要的形态描述。至于滇金丝猴和黔金丝猴牙齿的研究纯属空白。为此,有必要对这三个类群牙齿的形态结构作一个简要的比较观察,试图找出它们之间和属间的异同点,为今后的综合性探讨提供基本材料。  相似文献   
39.
K S Hui  Y J Wang  A Lajtha 《Biochemistry》1983,22(5):1062-1067
A membrane-bound aminopeptidase was purified from rat brain, and its activity was assayed by high-pressure liquid chromatography with Met-enkephalin as the substrate. The enzyme was extracted with 1% Triton X-100 and purified by chromatography, successively on DEAE-Sepharose CL-6B, Bio-Gel HTP, and Sephadex G-200 columns. The overall purification was about 1200-fold, with 25% yield. The purified enzyme showed one band on disc gel electrophoresis and two bands on sodium dodecyl sulfate electrophoresis with molecular weights of 62 000 and 66 000. The aminopeptidase has a pH optimum of 7.0, a Km of 0.28 mM, and a Vmax of 45 mumol (mg of protein)-1 min-1 for Met-enkephalin. It releases tyrosine from Met-enkephalin, but it does not split the byproduct. It does not hydrolyze gamma- or beta-endorphin, or dynorphin, but it does hydrolyze neutral and basic aminoacyl beta-naphthylamides. The enzyme is inhibited by the aminopeptidase inhibitors amastatin, bestatin, and bestatin-Gly. Its properties, such as its subcellular localization, substrate specificity, pH optimum, and molecular weight, distinguish it from leucine aminopeptidase, aminopeptidase A, aminopeptidase B, aminopeptidase M, and the soluble aminopeptidase for enkephalin degradation.  相似文献   
40.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号