全文获取类型
收费全文 | 2118篇 |
免费 | 136篇 |
专业分类
2254篇 |
出版年
2022年 | 8篇 |
2021年 | 23篇 |
2019年 | 15篇 |
2018年 | 20篇 |
2017年 | 15篇 |
2016年 | 36篇 |
2015年 | 70篇 |
2014年 | 90篇 |
2013年 | 87篇 |
2012年 | 141篇 |
2011年 | 152篇 |
2010年 | 103篇 |
2009年 | 86篇 |
2008年 | 124篇 |
2007年 | 127篇 |
2006年 | 145篇 |
2005年 | 126篇 |
2004年 | 131篇 |
2003年 | 134篇 |
2002年 | 105篇 |
2001年 | 22篇 |
2000年 | 21篇 |
1999年 | 20篇 |
1998年 | 23篇 |
1997年 | 29篇 |
1996年 | 32篇 |
1995年 | 18篇 |
1994年 | 16篇 |
1993年 | 17篇 |
1992年 | 27篇 |
1991年 | 13篇 |
1990年 | 17篇 |
1989年 | 18篇 |
1988年 | 14篇 |
1987年 | 15篇 |
1986年 | 16篇 |
1985年 | 9篇 |
1984年 | 13篇 |
1983年 | 9篇 |
1982年 | 14篇 |
1980年 | 13篇 |
1979年 | 16篇 |
1978年 | 5篇 |
1977年 | 8篇 |
1976年 | 12篇 |
1975年 | 8篇 |
1974年 | 5篇 |
1973年 | 7篇 |
1972年 | 9篇 |
1971年 | 10篇 |
排序方式: 共有2254条查询结果,搜索用时 10 毫秒
101.
Molecular structure of a novel cholesterol-responsive A subclass ABC transporter,ABCA9 总被引:2,自引:0,他引:2
Piehler A Kaminski WE Wenzel JJ Langmann T Schmitz G 《Biochemical and biophysical research communications》2002,295(2):408-416
We recently identified a novel ABC A subclass transporter, ABCA6, in human macrophages. Here, we report the molecular cloning of an additional ABC A subfamily transporter from macrophages denoted ABCA9. The identified coding sequence is 4.9 kb in size and codes for a 1624 amino acid protein product. In accordance with the proposed nomenclature, the novel transporter was designated ABCA9. The putative full-length ABC transporter polypeptide consists of two transmembrane domains and two nucleotide binding folds and thus conforms to the group of full-size ABC transporters. We identified alternative ABCA9 mRNA variants in human macrophages that predict the existence of three truncated forms of the novel transporter. Among the human ABC A subfamily transporters, ABCA9 exhibits the highest amino acid sequence homology with ABCA8 (72%) and ABCA6 (60%), respectively. The striking amino acid sequence similarity between these transporter molecules supports the notion that they represent an evolutionary more recently emerged subgroup within the family of ABC A transporters, which we refer to as "ABCA6-like transporters." ABCA9 mRNA is ubiquitously expressed with the highest mRNA levels in heart, brain, and fetal tissues. Analysis of the genomic structure revealed that the ABCA9 gene consists of 39 exons that are located within a genomic region of approximately 85 kb size on chromosome 17q24.2. In human macrophages, ABCA9 mRNA is induced during monocyte differentiation into macrophages and suppressed by cholesterol import indicating that ABCA9, like other known ABC A subfamily transporters, is a cholesterol-responsive gene. Based on this information, ABCA9 is likely involved in monocyte differentiation and macrophage lipid homeostasis. 相似文献
102.
Jacobi AM Hansen A Kaufmann O Pruss A Burmester GR Lipsky PE Dörner T 《Arthritis research》2002,4(4):R4
Patients with Sj?gren's syndrome (SS) have characteristic lymphocytic infiltrates of the salivary glands. To determine whether the B cells accumulating in the salivary glands of SS patients represent a distinct population and to delineate their potential immunopathologic impact, individual B cells obtained from the parotid gland and from the peripheral blood were analyzed for immunoglobulin light chain gene rearrangements by PCR amplification of genomic DNA. The productive immunoglobulin light chain repertoire in the parotid gland of the SS patient was found to be restricted, showing a preferential usage of particular variable lambda chain genes (V lambda 2E) and variable kappa chain genes (V kappa A27). Moreover, clonally related V(L) chain rearrangements were identified; namely, V kappa A27-J kappa 5 and V kappa A19-J kappa 2 in the parotid gland, and V lambda 1C-J lambda 3 in the parotid gland and the peripheral blood. V kappa and V lambda rearrangements from the parotid gland exhibited a significantly elevated mutational frequency compared with those from the peripheral blood (P < 0.001). Mutational analysis revealed a pattern of somatic hypermutation similar to that found in normal donors, and a comparable impact of selection of mutated rearrangements in both the peripheral blood and the parotid gland. These data indicate that there is biased usage of V(L) chain genes caused by selection and clonal expansion of B cells expressing particular V(L) genes. In addition, the data document an accumulation of B cells bearing mutated V(L) gene rearrangements within the parotid gland of the SS patient. These results suggest a role of antigen-activated and selected B cells in the local autoimmune process in SS. 相似文献
103.
Wartmann T Böer E Pico AH Sieber H Bartelsen O Gellissen G Kunze G 《FEMS yeast research》2002,2(3):363-369
The non-conventional dimorphic thermo- and salt-resistant yeast Arxula adeninivorans has been developed as a host for heterologous gene expression. For assessment of the system two model genes have been selected: the GFP gene encoding the intracellular green fluorescent protein, and the HSA gene encoding the secreted human serum albumin. The expression system includes two host strains, namely A. adeninivorans LS3, which forms budding cells at 30 degrees C and mycelia at >42 degrees C, and the strain A. adeninivorans 135, which forms mycelia at temperatures as low as 30 degrees C. For expression control the constitutive A. adeninivorans-derived TEF1-promoter and S. cerevisiae-derived PHO5-terminator were selected. The basic A. adeninivorans transformation/expression vector pAL-HPH1 is further equipped with the Escherichia coli-derived hph gene conferring hygromycin B resistance and the 25S rDNA from A. adeninivorans for rDNA targeting. Transformants were obtained for both budding cells and mycelia. In both cell types similar expression levels were achieved and the GFP was localised in the cytoplasm while more than 95% of the HSA accumulated in the culture medium. In initial fermentation trials on a 200-ml shake flask scale maximal HSA product levels were observed after 96 h of cultivation. 相似文献
104.
105.
Dournon C Membre H Brohm PE Coince A Cornu N Dreyer L Florentin J Jeanneau L Henniquin C Houbre M Guerard M Lecomte N Maxant L Schluraff M Venandet AS Jusyte A Simmet D Bocking D Flaig D Santak L Bolek S Goppel V Rossignon JP Trossat MA Raux M Forster S Staudenmaier G Boser S Horn E 《Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology》2002,9(1):P375-P376
The German-French biological experiment AQUARIUS-XENOPUS which flew on the Soyuz flight Andromede to the International Space Station ISS (launched October 21, 2001 in Baikonour/Kazakhstan) was extended by an outreach project. Pupils of class 10 to 12 from Ulm/D and Nancy-Tomblaine/F studied swimming behavior of Xenopus tadpoles on ground. They were instructed to perform all experimental steps following the protocol of similar video recordings on ISS. After the flight, they evaluated the kinetics of swimming of both ground controls and space animals. The pupil project included theoretical components to introduce them to the field of gravitational biology. One feature of the project was the exchange of ideas between pupils by meetings which took place in Ulm (June 2001), Nancy (February 2002) and Paris (May 2002). We consider our approach as a successful way to include young people in space experiments on a cheap cost level and to bring ideas of gravitational biology into the curricula of European schools. 相似文献
106.
107.
Reduced expression and increased CpG dinucleotide methylation of the rat APOBEC-1 promoter in transgenic rabbits 总被引:1,自引:0,他引:1
Editing of apolipoprotein (apo) B mRNA in liver limits the plasma LDL levels in horses, dogs, rats or mice. Species such as man or rabbit do not edit the hepatic apo B mRNA and are therefore susceptible to atherosclerosis and coronary artery disease due to elevated plasma LDL levels. The catalytic subunit APOBEC-1 is the only missing component of the apo B mRNA editing enzyme complex in the human or rabbit liver. Here we describe the generation of transgenic rabbits in which APOBEC-1 expression is mediated by the proximal promoter of the rat APOBEC-1 gene. These transgenic rabbits are healthy and fertile, and rat APOBEC-1 mRNA is expressed in liver, intestine, kidney, lung, brain and muscle. The transgenic APOBEC-1 expression is low and not sufficient to induce editing in rabbit liver. In rat, the proximal APOBEC-1 promoter demonstrates a progressive loss of CpG dinucleotide methylation towards the core promoter region that is entirely unmethylated. In the transgenic rabbits, this distinct pattern of CpG methylation is lost, and throughout the entire rat APOBEC-1 promoter, >90% of the CpGs are methylated. Thus, the weak proximal rat APOBEC-1 promoter appears to be down-regulated in the rabbit and may be species-specific. 相似文献
108.
The ATP binding cassette transporter A1 contributes to the secretion of interleukin 1beta from macrophages but not from monocytes 总被引:9,自引:0,他引:9
Zhou X Engel T Goepfert C Erren M Assmann G von Eckardstein A 《Biochemical and biophysical research communications》2002,291(3):598-604
Deficiency of ABCA1 causes high density lipoprotein deficiency and macrophage foam cell formation in Tangier disease. ABCA1 was also postulated to mediate the secretion of IL-1beta from monocytes and macrophages. We investigated the contribution of ABCA1 to IL-1beta secretion from human monocytes and macrophages of normal donors and Tangier disease patients. Neither an anti-ABCA1 antisense oligonucleotide nor ABCA1 deficiency interfered with LPS-induced secretion of IL-1beta from full blood or freshly isolated monocytes. By contrast, anti-ABCA1 antisense oligonucleotides decreased the LPS-induced secretion of IL-beta from macrophages by 30-50%. The secretion of the precursor pro-IL-1beta and TNFalpha was not inhibited. Compared to normal macrophages, LPS-stimulated Tangier disease macrophages secreted less IL-1beta relative to TNFalpha. Also the spontaneous secretion of IL-1beta by Tangier macrophages was lower than by control cells. We conclude that IL-1beta is secreted from monocytes by an ABCA1-independent pathway and from macrophages by ABCA1-dependent and -independent pathways. 相似文献
109.
110.
In flowering plants, maternal seed integument encloses the embryo and the endosperm, which are both derived from double fertilization. Although the development of these three components must be coordinated, we have limited knowledge of mechanisms involved in such coordination. The endosperm may play a central role in these mechanisms as epigenetic modifications of endosperm development, via imbalance of dosage between maternal and paternal genomes, affecting both the embryo and the integument. To identify targets of such epigenetic controls, we designed a genetic screen in Arabidopsis for mutants that phenocopy the effects of dosage imbalance in the endosperm. The two mutants haiku 1 and haiku 2 produce seed of reduced size that resemble seed with maternal excess in the maternal/paternal dosage. Homozygous haiku seed develop into plants indistinguishable from wild type. Each mutation is sporophytic recessive, and double-mutant analysis suggests that both mutations affect the same genetic pathway. The endosperm of haiku mutants shows a premature arrest of increase in size that causes precocious cellularization of the syncytial endosperm. Reduction of seed size in haiku results from coordinated reduction of endosperm size, embryo proliferation, and cell elongation of the maternally derived integument. We present further evidence for a control of integument development mediated by endosperm-derived signals. 相似文献