全文获取类型
收费全文 | 3996篇 |
免费 | 211篇 |
国内免费 | 235篇 |
专业分类
4442篇 |
出版年
2024年 | 20篇 |
2023年 | 67篇 |
2022年 | 108篇 |
2021年 | 112篇 |
2020年 | 106篇 |
2019年 | 120篇 |
2018年 | 132篇 |
2017年 | 85篇 |
2016年 | 122篇 |
2015年 | 250篇 |
2014年 | 278篇 |
2013年 | 332篇 |
2012年 | 162篇 |
2011年 | 178篇 |
2010年 | 141篇 |
2009年 | 203篇 |
2008年 | 199篇 |
2007年 | 216篇 |
2006年 | 174篇 |
2005年 | 181篇 |
2004年 | 179篇 |
2003年 | 138篇 |
2002年 | 120篇 |
2001年 | 84篇 |
2000年 | 72篇 |
1999年 | 75篇 |
1998年 | 74篇 |
1997年 | 68篇 |
1996年 | 54篇 |
1995年 | 55篇 |
1994年 | 48篇 |
1993年 | 44篇 |
1992年 | 28篇 |
1991年 | 30篇 |
1990年 | 32篇 |
1989年 | 28篇 |
1988年 | 18篇 |
1987年 | 22篇 |
1986年 | 12篇 |
1985年 | 9篇 |
1984年 | 19篇 |
1983年 | 12篇 |
1982年 | 12篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有4442条查询结果,搜索用时 13 毫秒
101.
Yu-Lu Wang Jue Wang Xiang Chen Zhi-Xin Wang Jia-Wei Wu 《Biochemical and biophysical research communications》2018,495(1):1-6
Sucrose non-fermenting (Snf1)-related kinase (SNRK) is a novel member of the AMP-activated protein kinase (AMPK) family and is involved in many metabolic processes. Here we report the crystal structure of an N-terminal SNRK fragment containing kinase and adjacent ubiquitin-associated (UBA) domains. This structure shows that the UBA domain binds between the N- and C-lobes of the kinase domain. The mode of UBA binding in SNRK largely resembles that in AMPK and brain specific kinase (BRSK), however, unique interactions play vital roles in stabilizing the KD-UBA interface of SNRK. We further propose a potential role of the UBA domain in the regulation of SNRK kinase activity. This study provides new insights into the structural diversities of the AMPK kinase family. 相似文献
102.
Paula Escuer Vadim A. Pisarenco Angel A. Fernndez-Ruiz Joel Vizueta Jose F. Snchez-Herrero Miquel A. Arnedo Alejandro Snchez-Gracia Julio Rozas 《Molecular ecology resources》2022,22(1):375-390
Here, we present the chromosome-level genome assembly of Dysdera silvatica Schmidt, 1981, a nocturnal ground-dwelling spider endemic from the Canary Islands. The genus Dysdera has undergone a remarkable diversification in this archipelago mostly associated with shifts in the level of trophic specialization, becoming an excellent model to study the genomic drivers of adaptive radiations. The new assembly (1.37 Gb; scaffold N50 of 174.2 Mb), was performed using the chromosome conformation capture scaffolding technique, represents a continuity improvement of more than 4500 times with respect to the previous version. The seven largest scaffolds or pseudochromosomes, which cover 87% of the total assembly size, probably correspond with the seven chromosomes of the karyotype of this species, including a characteristic large X chromosome. To illustrate the value of this new resource we performed a comprehensive analysis of the two major arthropod chemoreceptor gene families (i.e., gustatory and ionotropic receptors). We identified 545 chemoreceptor sequences distributed across all pseudochromosomes, with a notable underrepresentation in the X chromosome. At least 54% of them localize in 83 genomic clusters with a significantly lower evolutionary distances between them than the average of the family, suggesting a recent origin of many of them. This chromosome-level assembly is the first high-quality genome representative of the Synspermiata clade, and just the third among spiders, representing a new valuable resource to gain insights into the structure and organization of chelicerate genomes, including the role that structural variants, repetitive elements and large gene families played in the extraordinary biology of spiders. 相似文献
103.
蛋白酪氨酸磷酸酶PRL-3是近年发现的蛋白酪氨酸磷酸酶家族成员,能促进肿瘤细胞的侵袭、转移及上皮细胞间质转型,提示PRL-3可能在肿瘤发生发展及诱导肿瘤干细胞生成中发挥重要作用.由于侧群(SP)细胞具有许多干细胞的性质,SP细胞分选是目前筛选和分离获得干细胞或前体细胞常用的有效方法.为探讨PRL-3在诱导干细胞生成中的潜在作用,本文在建立过表达PRL-3的人胃癌细胞BGC823的基础上,通过SP分选和CCK-8的方法分析PRL-3对BGC823细胞中SP细胞的比例以及对化疗药物耐受性的影响.结果提示,高表达PRL-3提高BGC823中SP细胞的比例(2.5% vs 9.4%),同时增加BGC823对化疗药物紫杉醇和顺铂的耐受性(相对于对照细胞,其耐药指数分别为1.75和1.29).由于SP细胞的产生和细胞耐药性的提高与ABC家族基因表达水平上调密切相关,通过定量 RT-PCR和Western印迹检测发现,PRL-3能上调ABCB1和ABCG2的表达.上述研究结果表明,PRL-3有可能通过上调ABCB1和ABCG2的表达,增加胃癌细胞BGC823的SP细胞比例并增加其对化疗药物的耐受性. 相似文献
104.
Dual and simultaneous sensitivity analysis for matched pairs 总被引:1,自引:0,他引:1
105.
Animal tissues and organs are comprised of several types of cells, which are often arranged in a well-ordered pattern. The posterior part of the Drosophila wing margin is covered with a double row of long hairs, which are equally and alternately derived from the dorsal and ventral sides of the wing, exhibiting a zigzag pattern in the lateral view. How this geometrically regular pattern is formed has not been fully understood. In this study, we show that this zigzag pattern is created by rearrangement of wing margin cells along the dorsoventral boundary flanked by the double row of hair cells during metamorphosis. This cell rearrangement is induced by selective apoptosis of wing margin cells that are spatially separated from hair cells. As a result of apoptosis, the remaining wing margin cells are rearranged in a well-ordered manner, which shapes corrugated lateral sides of both dorsal and ventral edges to interlock them for zigzag patterning. We further show that the corrugated topology of the wing edges is achieved by cell-type specific expression and localization of four kinds of NEPH1/nephrin family proteins through heterophilic adhesion between wing margin cells and hair cells. Homophilic E-cadherin adhesion is also required for attachment of the corrugated dorsoventral edges. Taken together, our results demonstrate that sequential coordination of apoptosis and epithelial architecture with selective adhesion creates the zigzag hair alignment. This may be a common mechanism for geometrically ordered repetitive packing of several types of cells in similarly patterned developmental fields such as the mammalian organ of Corti. 相似文献
106.
XRN家族是一类5′-3′核酸外切酶家族,主要参与rRNA的成熟加工以及特异mRNA的降解过程,在动物、植物以及微生物的生长发育过程中起着重要的作用.对XRN家族在植物生长发育过程中的功能进行了综述,XRN家族在植物中主要参与rRNA加工过程、miRNA途径、外源mRNA降解过程以及乙烯信号通路. 相似文献
107.
108.
109.
The final reactions of rosmarinic acid biosynthesis, the introduction of the aromatic 3- and 3′-hydroxyl groups, are catalysed
by cytochrome P450-dependent hydroxylases. The cDNAs encoding CYP98A14 as well as a NADPH:cytochrome P450 reductase (CPR)
were isolated from Coleus blumei and actively expressed in Saccharomyces cerevisiae. The CYP98A14-cDNA showed an open reading frame of 1521 nucleotides with high similarities to 4-coumaroylshikimate/quinate
3-hydroxylases. Yeast microsomes harbouring the CYP98A14 protein catalysed the 3-hydroxylation of 4-coumaroyl-3′,4′-dihydroxyphenyllactate
and the 3′-hydroxylation of caffeoyl-4′-hydroxyphenyllactate, in both cases forming rosmarinic acid. Apparent K
m-values for 4-coumaroyl-3′,4′-dihydroxyphenyllactate and caffeoyl-4′-hydroxyphenyllactate were determined to be at 5 μM and
40 μM, respectively. CYP98A14 differs from CYP98s from other plants, since 4-coumaroylshikimate or -quinate were not accepted
as substrates. Coexpression of the Coleus blumei CPR and CYP98A14 in the same yeast cells increased the hydroxylation activity up to sevenfold. CYP98A14 from Coleus blumei is a novel bifunctional cytochrome P450 specialised for rosmarinic acid biosynthesis. 相似文献
110.
Hydroxyphenylpyruvate reductase (HPPR) is an enzyme involved in the biosynthesis of rosmarinic acid in Lamiaceae reducing hydroxyphenylpyruvates in dependence of NAD(P)H to the corresponding hydroxyphenyllactates. The HPPR protein was purified from suspension cells of Coleus blumei accumulating high levels of rosmarinic acid by ammonium sulfate precipitation, anion exchange chromatography, hydroxylapatite chromatography, chromatography on 2',5'-ADP-Sepharose 4B and SDS-polyacrylamide gel electrophoresis. The protein was tryptically digested and the peptides sequenced. Sequence information was used to isolate a full-length cDNA-clone for HPPR (EMBL accession number AJ507733) by RT-PCR, screening of a C. blumei cDNA-library and 5'-RACE-PCR. The open reading frame of the HPPR-cDNA consists of 939 nucleotides encoding a protein of 313 amino acid residues. The sequence showed that HPPR belongs to the family of D-isomer-specific 2-hydroxyacid dehydrogenases. The HPPR-cDNA was heterologously expressed in Escherichia coli and the protein was shown to catalyse the NAD(P)H-dependent reduction of 4-hydroxyphenylpyruvate to 4-hydroxyphenyllactate and 3,4-dihydroxyphenylpyruvate to 3,4-dihydroxyphenyllactate. 相似文献