全文获取类型
收费全文 | 13699篇 |
免费 | 1440篇 |
国内免费 | 2311篇 |
出版年
2024年 | 37篇 |
2023年 | 245篇 |
2022年 | 461篇 |
2021年 | 708篇 |
2020年 | 512篇 |
2019年 | 724篇 |
2018年 | 654篇 |
2017年 | 535篇 |
2016年 | 670篇 |
2015年 | 931篇 |
2014年 | 1113篇 |
2013年 | 1157篇 |
2012年 | 1372篇 |
2011年 | 1251篇 |
2010年 | 819篇 |
2009年 | 743篇 |
2008年 | 854篇 |
2007年 | 750篇 |
2006年 | 672篇 |
2005年 | 571篇 |
2004年 | 489篇 |
2003年 | 414篇 |
2002年 | 368篇 |
2001年 | 229篇 |
2000年 | 188篇 |
1999年 | 162篇 |
1998年 | 121篇 |
1997年 | 97篇 |
1996年 | 75篇 |
1995年 | 46篇 |
1994年 | 54篇 |
1993年 | 34篇 |
1992年 | 48篇 |
1991年 | 43篇 |
1990年 | 52篇 |
1989年 | 33篇 |
1988年 | 19篇 |
1987年 | 18篇 |
1986年 | 30篇 |
1985年 | 16篇 |
1984年 | 17篇 |
1983年 | 20篇 |
1982年 | 12篇 |
1981年 | 14篇 |
1980年 | 7篇 |
1979年 | 17篇 |
1978年 | 6篇 |
1977年 | 9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 125 毫秒
971.
我国沿海缢蛏群体遗传结构的mtDNA-COⅠ分析 总被引:2,自引:0,他引:2
采集了我国沿海共计9个缢蛏(Sinonovacula constricta)地理群体的197个样本,分别是北部组群的3个群体:辽宁省庄河群体(ZH),天津市汉沽群体(HG),山东省海阳群体(HY);中部组群的3个群体:江苏省盐城群体(YC),上海市崇明县东滩群体(DT)和堡镇群体(BZ);以及南部组群的3个群体:浙江省宁波群体(NB),浙江省台州群体(TZ)以及福建省宁德群体(ND)。利用线粒体COⅠ标记分析了9个群体的遗传多样性和遗传分化。结果表明,在共计197个个体中检测到125个单倍型和96个变异位点,核苷酸多样性指数位于2.1764~7.4970之间,其中中部组群的群体遗传多样性指数最高。AMOVA分析结果显示,组间遗传变异量占总变异的80.27%,18.74%来自于群体内,只有0.99%来自于组内群体间。群体间遗传分化系数位于0.0219~0.8706之间,不同群体间具有一定的遗传分化,尤其是中部群体与其他群体间遗传分化值达到了0.8以上,为极高度分化。遗传距离和聚类结果显示,北部3群体和南部3群体首先聚在一起,之后与中部3群体聚类。 相似文献
972.
微卫星技术在大耳白黑眼兔近交系培育中的监测分析 总被引:1,自引:0,他引:1
利用微卫星技术监测大耳白黑眼兔(white hair black eyes rabbits,WHBE兔)近交培育中第五代(F5)、第六代(F6)和第七代(F7)的遗传多样性.选取21个微卫譬座位,筛选出扩增产物稳定并且具有多态性的11对微卫星引物用于本研究.结果表明,F5代WHBE兔在每个座位上的等位基因数(Na)为3~9个不等,11个座位的平均有效等位基因数(Ne)为1.81个,平均观察杂合度(Ho)和平均多态信息含量(PIC)分别为0.381和0.524,累积个体识别率(CDP)达到100%,累积非父排除概率(CPE)在双亲信息都是未知情况下的为0.926,而在得知任一亲本信息的情况F,CPE值为0.993.F6代WHBE兔在每个座位上的Na为3~8个不等,11个座位的平均Ne为1.68个,平均Ho和PIC值分别为0.356和0.548,CDP达到100%,CPE在双亲信息都是未知情况下的为0.931,而在得知任一亲本信息的情况下,CPE值为0.994.F7代WHBE兔在每个座位上的Na为2~6个不等,11个座位的Ne为1.51个,平均Ho和PIC值分别为0.287和0.498,CDP达到100%,CPE在双亲信息都是未知情况下的为0.891,而在得知任一亲本信息的情况下,CPE值为0.986.在近交系培育过程中,从F5代到F7代,WHBE兔的平均Ne和平均Ho 都呈下降趋势,提示随着近交代数的增加,WHBE兔的基因纯合度越来越高. 相似文献
973.
Overaccumulation of glycine betaine enhances tolerance of the photosynthetic apparatus to drought and heat stress in wheat 总被引:3,自引:0,他引:3
To investigate the role of glycine betaine in photosynthesis under stress, a transgenic wheat (Triticum aestivum L.) line T6 overaccumulating glycine betaine and its wild type Shi4185 were used. Seedlings were exposed to conditions of
drought (30%, PEG-6000), heat (40°C) and their combination. The results revealed ultrastructural damage to the chloroplast
and thylakoid lamellae with the withered phenotype by both drought and heat stress, and the damage was exacerbated by the
combination of drought and heat. The appearance of a K step in the typical O-J-I-P curve and the decrease of Hill activity
indicated a reduction of oxygen evolving complex function caused by stress. The greater damage was found in wild type than
T6. Overaccumulation of glycine betaine in T6 could protect lipids in the thylakoid membrane from damage and stabilize the
index of unsaturated fatty acids under stress. A lower ratio of monogalactosyl diacylglycerol/digalactosyl diacylglycerol
and higher phosphatidylglycerol content in the thylakoid membrane of T6 were also observed under stress. These effects can
promote stability of the thylakoid membrane. Otherwise, glycine betaine overaccumulation decreased photoinhibition of PSII
under stress. The results also suggest that xanthophyll cycle-dependent non-radiative energy dissipation may be involved in
the GB-mediated effects on PSII function under stress conditions. 相似文献
974.
Xiaoqing Guo Liwei Zhang Mingli Wu Na Wang Yanfeng Liu Limian Er Shunping Wang Yang Gao Weifang Yu Hui Xue Zhibin Xu Shijie Wang 《Molecular biology reports》2010,37(1):219-225
DNMT3B is an important enzyme to modulate the methylation status in mammalian cells. The aim of this study is to investigate the correlation of the DNMT3B G39179T polymorphism with the susceptibilities of colorectal adenomatous polyps and adenocarcinoma. This case-control study included 146 colorectal adenomatous polyps, 170 colorectal adenocarcinoma patients, and 157 normal controls. DNMT3B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Family history of colorectal cancer significantly increases the risk of developing colorectal adenomatous polyps and adenocarcinoma. The genotype frequency of DNMT3B polymorphism (T/T and G/T + G/G) in adenocarcinoma patients was significantly different from that in controls (P value = 0.01). Compared with DNMT3B T/T genotype, the G allelotype (G/T + G/G genotype) had lower risk to develop colorectal adenocarcinoma (OR = 0.50, 95% CI = 0.29–0.87); while there was no significant difference between the colorectal adenomatous polyps patients and controls (OR = 0.63, 95% CI = 0.37–1.09), although descending tendency could be found in this polyps group. In the stratification analysis, a significant association was confined to subgroups of age < 55 (OR = 0.31, 95% CI = 0.12–0.84) and males (OR = 0.35, 95% CI = 0.17–0.71). Meanwhile, combined G/T + G/G genotypes were found to have a lower risk in non-drinkers to develop both colorectal adenomatous polyps and adenocarcinoma (OR = 0.54, 95% CI = 0.31–0.96 and OR = 0.48, 95% CI = 0.27–0.84, respectively). This study also showed a distinct difference in the distribution of DNMT3B G39179T SNP in different ethnics. DNMT3B G39179T SNP may be a potential genetic susceptibility factor for adenocarcinoma of the colon, especially in younger Chinese Han non-drinker men. 相似文献
975.
Yi Liang Jia Cheng Lin Kun Wang Yi Jie Chen Hong Hong Liu Rong Luan Shuai Jiang Tao Che Yong Zhao De Feng Li Da Cheng Wang Lin Guo Hui Sun 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
We have previously reported a novel fungal galectin Agrocybe aegerita lectin (AAL) with apoptosis-induced activity and nuclear migration activity. The importance of nuclear localization for AAL's apoptosis-induced activity has been established by mutant study. However, the mechanism remains unclear.Methods
We further investigated the mechanism using a previously reported carbohydrate recognition domain (CRD) mutant protein H59Q, which retained its nuclear localization activity but lost most of its apoptotic activity. The cell membrane-binding ability of recombinant AAL (rAAL) and H59Q was analyzed by FACS, and their cellular partners were identified by affinity chromatography and mass spectroscopy. Furthermore, the interaction of AAL and ligand was proved by mammalian two-hybrid and pull down assays. A knockdown assay was used to confirm the role of the ligand.Results
The apoptotic activity of AAL could be blocked by lactose. Mutant H59Q retained comparable cell membrane-binding ability to rAAL. Four cellular binding partners of AAL in HeLa cells were identified: glucose-regulated protein 78 (GRP78); mortality factor 4-like protein 1 (MRG15); elongation factor 2 (EEF2); and heat shock protein 70 (Hsp70). CRD region of AAL was required for the interaction between AAL/mutant AAL and MRG15. MRG15 knockdown increased the cells' resistance to AAL treatment.Conclusion
MRG15 was a nuclear ligand for AAL in HeLa cells. These data implied the existence of a novel nuclear pathway for the antitumor activity of fungal galectin AAL.General significance
These findings provide a novel explanation of AAL bioactivity and contribute to the understanding of mushroom lectins' antitumor activity. 相似文献976.
977.
Fang Z Fang W Liu J Hong Y Peng H Zhang X Sun B Xiao Y 《Journal of microbiology and biotechnology》2010,20(9):1351-1358
The demand for beta-glucosidases insensitive to product inhibition is increasing in modern biotechnology, for these enzymes would improve the process of saccharification of lignocellulosic materials. In this study, a beta-glucosidase gene which encodes a 442-amino-acid protein was isolated from a marine microbial metagenomic library by functional screening and named as bgl1A. The protein was identified to be a member of GH1 family, and was recombinantly expressed, purified and biochemically characterized. The recombinant beta-glucosidase, Bgl1A, exhibited high level of stability in the presence of various cations and high concentrations of NaCl. Interestingly, it was activated by glucose at concentrations lower than 400 mM. With glucose further increasing, the enzyme activity of Bgl1A was gradually inhibited, but remained 50% original value in even as high as 1,000 mM glucose. These findings indicate Bgl1A might be a potent candidate for industrial applications. 相似文献
978.
The popular view that plant mitochondrial genome evolves slowly in sequence has been recently challenged by the extraordinarily high substitution rates of mtDNA documented mainly from several angiosperm genera, but high substitution rate acceleration accompanied with great length variation has been very rarely reported in plant mitochondrial genes. Here, we studied evolution of the mitochondrial rps3 gene that encodes the ribosomal small subunit protein 3 and found a dramatically high variation in both length and sequence of an exon region of it in Conifer II. A sequence comparison between cDNA and genomic DNA showed that there are no RNA editing sites in the Conifer II rps3 gene. Southern blotting analyses of the total DNA and mtDNA, together with the real-time PCR analysis, showed that rps3 exists as a single mitochondrial locus in gymnosperms. It is very likely that the Conifer II rps3 gene has experienced retroprocessing, i.e., the re-integration of its cDNA into the mitochondrial genome, followed by an evolutionary acceleration due to the intron loss. In addition, the phylogenetic analysis of rps3 supports the sister relationship between conifers and Gnetales. In particular, the monophyly of conifer II is strongly supported by the shared loss of two rps3 introns. Our results also indicate that the mitochondrial gene tree would be affected in topology when the “edited” paralogs are analyzed together with their genomic sequences. 相似文献
979.
Zhen Zhang Enfu Hui Edwin R. Chapman Meyer B. Jackson 《Molecular biology of the cell》2010,21(16):2821-2831
Synaptotagmin (syt) serves as a Ca2+ sensor in the release of neurotransmitters and hormones. This function depends on the ability of syt to interact with other molecules. Syt binds to phosphatidylserine (PS)-containing lipid bilayers as well as to soluble N-ethylmaleimide sensitive factor receptors (SNAREs) and promotes SNARE assembly. All these interactions are regulated by Ca2+, but their specific roles in distinct kinetic steps of exocytosis are not well understood. To explore these questions we used amperometry recording from PC12 cells to investigate the kinetics of exocytosis. Syt isoforms and syt I mutants were overexpressed to perturb syt-PS and syt-SNARE interactions to varying degrees and evaluate the effects on fusion event frequency and the rates of fusion pore transitions. Syt I produced more rapid dilation of fusion pores than syt VII or syt IX, consistent with its role in synchronous synaptic release. Stronger syt-PS interactions were accompanied by a higher frequency of fusion events and more stable fusion pores. By contrast, syt-SNARE interactions and syt-induced SNARE assembly were uncorrelated with rates of exocytosis. This associates the syt-PS interaction with two distinct kinetic steps in Ca2+ triggered exocytosis and supports a role for the syt-PS interaction in stabilizing open fusion pores. 相似文献
980.
Xiaojuan Sun Hui He Zhihui Xie Weiping Qian Haiyen E. Zhau Leland W. K. Chung Fray F. Marshall Ruoxiang Wang 《In vitro cellular & developmental biology. Animal》2010,46(6):538-546
Prostate stromal cells may play binary roles in the process of prostate cancer development. As the first to be encountered
by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression
and metastasis. However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment
favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer
and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal clones. In this
report, we describe the morphologic and behavioral characteristics of these cells and their effect on LNCaP prostate cancer
cells in co-culture. Unlike LNCaP prostate cancer cells, the isolated prostate stromal clones are large fibroblast-like cells
with a slow proliferation rate. Growth and survival of these clones are not affected by androgens. The stromal cells display
high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability. In co-culture
experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated
stromal clones showed more protection. This work thus established a panel of valuable human prostate stromal cell lines, which
could be used in co-culture to study the interaction between prostate cancer and prostate stromal cells. 相似文献