全文获取类型
收费全文 | 298篇 |
免费 | 90篇 |
国内免费 | 32篇 |
出版年
2022年 | 6篇 |
2021年 | 4篇 |
2020年 | 6篇 |
2019年 | 4篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 8篇 |
2014年 | 10篇 |
2013年 | 9篇 |
2012年 | 16篇 |
2011年 | 24篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 12篇 |
2007年 | 15篇 |
2006年 | 9篇 |
2005年 | 14篇 |
2004年 | 9篇 |
2003年 | 7篇 |
2002年 | 18篇 |
2000年 | 7篇 |
1999年 | 15篇 |
1998年 | 6篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 10篇 |
1981年 | 9篇 |
1980年 | 6篇 |
1979年 | 10篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1970年 | 3篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1966年 | 3篇 |
1965年 | 3篇 |
1932年 | 3篇 |
排序方式: 共有420条查询结果,搜索用时 15 毫秒
61.
VLJ Whitehall TD Dumenil DM McKeone CE Bond ML Bettington RL Buttenshaw L Bowdler GW Montgomery LF Wockner BA Leggett 《Epigenetics》2014,9(11):1454-1460
The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features. 相似文献
62.
目的:研究双源CT冠状动脉血管成像诊断心肌桥的临床价值。方法:选择260例具有典型心前区不适的患者进行双源CT冠脉血管成像检查,观察其发生部位,测量其长度和深度并进行分析。结果:260例受检患者中,62例共70段存在心肌桥,检出率达20.76%,高于文献报道的检出率18.2%。所有心肌桥均发生于左前降支,其中近段17段(24.4%),中段43段(61.4%),远段10段(14.2%)。心肌桥平均长度为15.8±6.4mm,深度为1.4±0.85mm。结论:双源CT冠状动脉血管成像因其便捷无创,不受心率严格限制且价格低廉可作为心肌桥筛查的理想检查手段。 相似文献
63.
Bethany J. Wilcox Jonathan G. Beckwith Richard M. Greenwald Jeffrey J. Chu Thomas W. McAllister Laura A. Flashman Arthur C. Maerlender Ann-Christine Duhaime Joseph J. Crisco 《Journal of biomechanics》2014
The purpose of this study was to quantify head impact exposure (frequency, location and magnitude of head impacts) for individual male and female collegiate ice hockey players and to investigate differences in exposure by sex, player position, session type, and team. Ninety-nine (41 male, 58 female) players were enrolled and 37,411 impacts were recorded over three seasons. Frequency of impacts varied significantly by sex (males: 287 per season, females: 170, p<0.001) and helmet impact location (p<0.001), but not by player position (p=0.088). Head impact frequency also varied by session type; both male and female players sustained more impacts in games than in practices (p<0.001), however the magnitude of impacts did not differ between session types. There was no difference in 95th percentile peak linear acceleration between sexes (males: 41.6 g, females: 40.8 g), but 95th percentile peak rotational acceleration and HITsp (a composite severity measure) were greater for males than females (4424, 3409 rad/s2, and 25.6, 22.3, respectively). Impacts to the back of the helmet resulted in the greatest 95th percentile peak linear accelerations for males (45.2 g) and females (50.4 g), while impacts to the side and back of the head were associated with the greatest 95th percentile peak rotational accelerations (males: 4719, 4256 rad/sec2, females: 3567, 3784 rad/sec2 respectively). It has been proposed that reducing an individual's head impact exposure is a practical approach for reducing the risk of brain injuries. Strategies to decrease an individual athlete's exposure need to be sport and gender specific, with considerations for team and session type. 相似文献
64.
65.
Use of gene fusion to study secretion of maltose-binding protein into Escherichia coli periplasm. 总被引:31,自引:32,他引:31
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We have employed the technique of gene fusion to fuse the LacZ gene encoding the cytoplasmic enzyme beta-galactosidase with the malE gene encoding the periplasmic maltose binding protein (MBP). Strains were obtained which synthesize malE-lacZ hybrid proteins of various sizes. These proteins have, at their amino terminus, a portion of the MBP and at their carboxyl terminus, enzymatically active beta-galactosidase. When the hybrid protein includes only a small, amino-terminal portion of the MBP, the hybrid protein residues in the cytoplasm. When the hybrid protein contains enough of the MBP to include an intact MBP signal sequence, a significant portion of the hybrid protein is found in the cytoplasmic membrane, suggesting that secretion of the hybrid protein has been initiated. However, in no case is the hybrid protein secreted into the periplasm, even when the hybrid protein includes almost the entire MBP. In the latter case, the synthesis and attempted export of the hybrid protein interferes with the export of at least certain normal envelope proteins, which accumulate in the cell in their precursor forms, and the cell dies. These results suggest that a number of envelope proteins may be exported at a common site, and that there are only a limited number of such sites. Also, these results indicate that it is not sufficient to simply attach an amino-terminal signal sequence to a polypeptide to assure its export. 相似文献
66.
67.
目的:探讨MR弥散加权成像(DWI)鉴别诊断良恶性椎体压缩性骨折的临床价值。方法:对57例经临床或病理证实的椎体良恶性压缩性骨折患者行矢状位T1M、T2WI、T2WI/FS及DWI扫描,研究其在常规序列和DWI序列上的表现,将常规MR序列和DWI序列检出率进行比较,测量正常椎体及病变椎体的表观弥散系数(ADC)值,并进行统计学分析。结果:(1)MR常规序列和DWI序列(b=500s/mm2)表现:良性椎体压缩性骨折呈长T1长或等T2改变,T2WI/FS呈高信号,DWI可以呈高信号、等信号及低信号;恶性椎体压缩性骨折呈长T1长T2信号,大部分病灶T2WUFS及DWI呈高信号,少数变现为低信号;(2)MR常规序列和DWI序列(b=500s/mm2)病灶检出率的比较:T1WI、T2WI/FS及DWI序列病灶检出率均高于T2WI序列,其间的差别有显著性意义(P〈0.01),T1WI、T2WI/FS及DWI序列病灶检出率之间无显著性差异(P〉0.01);(3)ADC值比较:在DWI(b=500s/mm2)上,良性组ADC值为(2.03±0.83)×10^3mm^2/s,恶性组ADC值为(1.37±0.75)×10^-3mm^2/s,正常组ADC值为(0.36±0.21)×10^-3mm^2/s,成像条件相同时,良性组高于恶性组,两组间有明显的统计学意义(P〈0.05)。结论:DWI可较好的反映椎体的弥散特征,ADC值作为量化指标可对良恶性椎体压缩性骨折进行可靠鉴别。 相似文献
68.
黑皮质素系统来自阿片-促黑素细胞皮质素原,在中枢摄食行为和能量平衡代谢中起到重要作用,此系统生理功能的发挥主要通过与下丘脑神经元细胞上特定膜受体(黑皮质素受体)结合完成。黑皮质素受体(MCR)有五种亚型(MC1R-MC5R),其中参与体重调节的受体主要是黑皮质素受体3(MC3R)和黑皮质素受体4(MC4R)。MC4R属于G蛋白耦联受体,具有七次跨膜结构。作为一种膜受体,MC4R发挥体重调节作用,一方面受外界激动剂或拮抗剂的调节;另一方面,此受体活化后会影响到细胞内的信号调节通路。研究MC4R的功能首先要了解受体的结构,本文对G蛋白耦联受体的结构进行了较详细的叙述,MC4R经信号调节通路,激活腺苷酸环化酶,增加cAMP的浓度,最终通过影响细胞内基因的转录和翻译,来调节体重和能量的消耗。 相似文献
69.
Alpha-MSH has a wide variety of putative biological activities in addition to its classical melanocyte dispersing activity. Since each of these activities appears to be mediated by a discrete receptor, this peptide is an excellent candidate for exploring conformational restrictions which determine the chemical-physical basis for hormone action on specific activities. Experiments One and Two evaluated several cyclic and linear analogs of alpha-MSH on retrieval of memory during the reactivation of memory for a passive avoidance response following hypothermia-induced amnesia. Three of the cyclic analogs appear to have enhanced the peptide's ability to serve as a reactivation agent. One of the linear Nle4,D-Phe7 analogs antagonized whereas three others enhanced reactivation. The D-Phe7 substitution in cyclic analogs did not affect reactivation. Another group of animals were trained on a step-through passive avoidance task and tested 25 days later. The cyclic analog enhanced memory whereas the D-Phe7 analog and alpha-MSH had no effect. Finally, two analogs were tested on a black-white discrimination. Although the cyclic analog had no effect on either acquisition or reversal of this learning, the Nle4,D-Phe7 analog significantly impaired reversal learning. The results from these preliminary studies suggest that structural modifications of alpha-MSH do alter its potency and pattern of actions in learning and memory situations. 相似文献
70.
莲藕干物质和氮磷钾养分的累积与分配研究 总被引:1,自引:0,他引:1
连续2年采用盆栽试验研究了莲藕(Nelumbo nucifera Gaertn)干物质和氮磷钾养分的累积与分配规律。结果表明:莲藕苗期以叶片生长并积累光合产物为主,膨大根状茎成型后,叶片、叶柄和根状茎中的干物质不断运输并贮存到膨大根状茎中,以产量形成为主,干物质累积总量增长呈"慢-快-稳定"的变化趋势;氮磷钾累积量与干物质累积量变化趋势一致,并与之呈极显著正相关,莲藕氮磷钾养分累积总量之比为1∶0.12∶1.31。移栽后97-160 d是莲藕产量形成的关键时期,不仅叶片、叶柄和根状茎中的氮磷钾随同干物质运输并贮存到膨大根状茎中,根系还从土壤中吸收更多的氮磷钾直接运输并贮存到膨大根状茎中,后者分别占同期氮磷钾累积量的69.8%、79.2%和75.0%。160 d膨大根状茎中干物质、氮、磷和钾累积量分别平均占植株总累积量的81.1%、85.2%、88.8%和80.2%。 相似文献