全文获取类型
收费全文 | 2895篇 |
免费 | 308篇 |
国内免费 | 197篇 |
出版年
2023年 | 22篇 |
2022年 | 22篇 |
2021年 | 91篇 |
2020年 | 65篇 |
2019年 | 64篇 |
2018年 | 64篇 |
2017年 | 62篇 |
2016年 | 88篇 |
2015年 | 175篇 |
2014年 | 169篇 |
2013年 | 198篇 |
2012年 | 269篇 |
2011年 | 253篇 |
2010年 | 141篇 |
2009年 | 141篇 |
2008年 | 179篇 |
2007年 | 185篇 |
2006年 | 162篇 |
2005年 | 150篇 |
2004年 | 115篇 |
2003年 | 102篇 |
2002年 | 105篇 |
2001年 | 46篇 |
2000年 | 35篇 |
1999年 | 46篇 |
1998年 | 34篇 |
1997年 | 18篇 |
1996年 | 16篇 |
1994年 | 18篇 |
1993年 | 9篇 |
1992年 | 15篇 |
1991年 | 21篇 |
1990年 | 15篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 14篇 |
1985年 | 12篇 |
1984年 | 15篇 |
1983年 | 19篇 |
1982年 | 11篇 |
1981年 | 12篇 |
1979年 | 9篇 |
1978年 | 11篇 |
1977年 | 14篇 |
1974年 | 12篇 |
1973年 | 13篇 |
1972年 | 9篇 |
1971年 | 10篇 |
1970年 | 9篇 |
1968年 | 8篇 |
排序方式: 共有3400条查询结果,搜索用时 70 毫秒
101.
上升流和水团对浙江中部近海浮游动物生态类群分布的影响 总被引:9,自引:1,他引:8
依据2010年4月、7月和11月对浙江中部近海上升流海域进行的海洋调查资料,运用定量、定性方法,探讨了上升流对该海域浮游动物生态类群分布的影响.结果表明:3个季节共鉴定浮游动物64种,桡足类占主要优势,包括5个生态类群,分别是暖温带近海种、暖温带外海种、亚热带近海种、亚热带外海种和热带大洋种.在种类数组成上,春季以暖温带近海种为主,夏季则是亚热带近海种和亚热带外海种居多,秋季也是亚热带种居多,其中夏季暖温带种种类数要高于春季和秋季,这一现象与同时期东黄海沿海有所不同,主要是由于上升流将一些在海洋底部度夏的暖温种带至海洋表面造成的.此外,3个季节生态类群都是以近海种为主,表明沿岸流是影响这一海域的最主要的水团.在丰度组成上,4月暖温带近海种占总丰度的98.79%,7月暖温带近海种也是组成丰度的重要部分,10月则是亚热带近海种丰度最高.丰度组成所反映的规律与种类数组成规律一致.上升流的存在导致夏季近海暖温带种大量出现,是影响这一海域浮游动物生态类群组成的重要因素;受长江径流和椒江径流的影响,近海种成为主要生态类群,是这一海域浮游动物的一个重要的生态特征. 相似文献
102.
Mira B. MacLennan Shannon E. Clarke Kate Perez Geoffrey A. Wood William J. Muller Jing X. Kang David W.L. Ma 《The Journal of nutritional biochemistry》2013,24(1):388-395
IntroductionDespite the advocacy that diet may be a significant contributor to cancer prevention, there is a lack of direct evidence from epidemiological and experimental studies to substantiate such claims. Experimental studies suggest that n-3 polyunsaturated fatty acids (n-3 PUFA) from marine oils may reduce breast cancer risk, however, findings are equivocal. Thus, in this study, novel transgenic mouse models were employed to provide, for the first time, direct evidence for an anti-cancer role of n-3 PUFA in mammary tumorigenesis.Methodsfat-1 Mice, which are capable of endogenous n-3 PUFA synthesis, were bred with mouse mammary tumor virus (MMTV)-neu(ndl)-YD5 mice, an aggressive breast cancer model. The resultant offspring, including novel hybrid progeny, were assessed for tumor onset, size and multiplicity as well as n-3 PUFA composition in mammary gland and tumor tissue. A complementary group of MMTV-neu(ndl)-YD5 mice were fed n-3 PUFA in the diet.ResultsMice expressing MMTV-neu(ndl)-YD5 and fat-1 displayed significant (P<.05) reductions in tumor volume (~30%) and multiplicity (~33%), as well as reduced n-6 PUFA and enriched n-3 PUFA in tumor phospholipids relative to MMTV-neu(ndl)-YD5 control mice. The effect observed in hybrid progeny was similarly observed in n-3 PUFA diet fed mice.ConclusionUsing complementary genetic and conventional dietary approaches we provide, for the first time, unequivocal experimental evidence that n-3 PUFA is causally linked to tumor prevention. 相似文献
103.
目的探讨胃息肉与幽门螺杆菌(Helicobacter pylori,H.pylori)感染关系。方法对1218例胃息肉同时进行H.pylori检查患者进行回顾性分析,分析胃息肉患者H.pylori感染率、胃息肉部位与H.pylori感染关系、胃息肉病理类型与H.pylori感染关系。结果发现胃息肉Hpylori感染患者532例,Hpylori感染率为43.7%。男性胃息肉患者H.pylori感染率为47.5%(216/455),女性Hpriori感染率感染率为41.4%(316/763)(P〉0.05),年龄〈20岁、20~39岁、40—59岁和≥60岁胃息肉H.priori感染率分别为41.7%、44.7%、41.6%和47.2%(P〉0.05);胃窦胃角息肉H.pylori感染率高于其他部位(胃体、胃底和贲门)(P〈0.05);炎性和增生性胃息肉H.priori感染率高于胃底腺和腺瘤性息肉(P〈0.05)。结论H.pylori感染可能与部分胃息肉发生有一定关系,需要进一步深入研究胃息肉的发生机制。 相似文献
104.
105.
Christine N. Kay Renee C. Ryals George V. Aslanidi Seok Hong Min Qing Ruan Jingfen Sun Frank M. Dyka Daniel Kasuga Andrea E. Ayala Kim Van Vliet Mavis Agbandje-McKenna William W. Hauswirth Sanford L. Boye Shannon E. Boye 《PloS one》2013,8(4)
Development of viral vectors capable of transducing photoreceptors by less invasive methods than subretinal injection would provide a major advancement in retinal gene therapy. We sought to develop novel AAV vectors optimized for photoreceptor transduction following intravitreal delivery and to develop methodology for quantifying this transduction in vivo. Surface exposed tyrosine (Y) and threonine (T) residues on the capsids of AAV2, AAV5 and AAV8 were changed to phenylalanine (F) and valine (V), respectively. Transduction efficiencies of self-complimentary, capsid-mutant and unmodified AAV vectors containing the smCBA promoter and mCherry cDNA were initially scored in vitro using a cone photoreceptor cell line. Capsid mutants exhibiting the highest transduction efficiencies relative to unmodified vectors were then injected intravitreally into transgenic mice constitutively expressing a Rhodopsin-GFP fusion protein in rod photoreceptors (Rho-GFP mice). Photoreceptor transduction was quantified by fluorescent activated cell sorting (FACS) by counting cells positive for both GFP and mCherry. To explore the utility of the capsid mutants, standard, (non-self-complementary) AAV vectors containing the human rhodopsin kinase promoter (hGRK1) were made. Vectors were intravitreally injected in wildtype mice to assess whether efficient expression exclusive to photoreceptors was achievable. To restrict off-target expression in cells of the inner and middle retina, subsequent vectors incorporated multiple target sequences for miR181, an miRNA endogenously expressed in the inner and middle retina. Results showed that AAV2 containing four Y to F mutations combined with a single T to V mutation (quadY−F+T−V) transduced photoreceptors most efficiently. Robust photoreceptor expression was mediated by AAV2(quadY−F+T−V) −hGRK1−GFP. Observed off-target expression was reduced by incorporating target sequence for a miRNA highly expressed in inner/middle retina, miR181c. Thus we have identified a novel AAV vector capable of transducing photoreceptors following intravitreal delivery to mouse. Furthermore, we describe a robust methodology for quantifying photoreceptor transduction from intravitreally delivered AAV vectors. 相似文献
106.
Souriya Vang Hsin-Ta Wu Andrew Fischer Daniel H. Miller Shannon MacLaughlan Elijah Douglass Margaret Steinhoff Colin Collins Peter J. S. Smith Laurent Brard Alexander S. Brodsky 《PloS one》2013,8(3)
Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease. 相似文献
107.
Calcium (Ca) sparks are the fundamental sarcoplasmic reticulum (SR) Ca release events in cardiac myocytes, and they have a typical duration of 20–40 ms. However, when a fraction of ryanodine receptors (RyRs) are blocked by tetracaine or ruthenium red, Ca sparks lasting hundreds of milliseconds have been observed experimentally. The fundamental mechanism underlying these extremely prolonged Ca sparks is not understood. In this study, we use a physiologically detailed mathematical model of subcellular Ca cycling to examine how Ca spark duration is influenced by the number of functional RyRs in a junctional cluster (which is reduced by tetracaine or ruthenium red) and other SR Ca handling properties. One RyR cluster contains a few to several hundred RyRs, and we use a four-state Markov RyR gating model. Each RyR opens stochastically and is regulated by cytosolic and luminal Ca. We varied the number of functional RyRs in the single cluster, diffusion within the SR network, diffusion between network and junctional SR, cytosolic Ca diffusion, SERCA uptake activity, and RyR open probability. For long-lasting Ca release events, opening events within the cluster must occur continuously because the typical open time of the RyR is only a few milliseconds. We found the following: 1) if the number of RyRs is too small, it is difficult to maintain consecutive openings and stochastic attrition terminates the release; 2) if the number of RyRs is too large, the depletion of Ca from the junctional SR terminates the release; and 3) very long release events require relatively small-sized RyR clusters (reducing flux as seen experimentally with tetracaine) and sufficiently rapid intra-SR Ca diffusion, such that local junctional intra-SR [Ca] can be maintained by intra-SR diffusion and overall SR Ca reuptake. 相似文献
108.
Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology 总被引:1,自引:0,他引:1
Marcela Montes de Oca Rajiv Kumar Fabian de Labastida Rivera Fiona H Amante Meru Sheel Rebecca J. Faleiro Patrick T. Bunn Shannon E. Best Lynette Beattie Susanna S. Ng Chelsea L. Edwards Werner Muller Erika Cretney Stephen L. Nutt Mark J. Smyth Ashraful Haque Geoffrey R. Hill Shyam Sundar Axel Kallies Christian R. Engwerda 《PLoS pathogens》2016,12(1)
Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation. 相似文献
109.
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
110.
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