全文获取类型
收费全文 | 1211篇 |
免费 | 113篇 |
专业分类
1324篇 |
出版年
2022年 | 13篇 |
2021年 | 14篇 |
2020年 | 12篇 |
2019年 | 16篇 |
2018年 | 18篇 |
2017年 | 21篇 |
2016年 | 25篇 |
2015年 | 43篇 |
2014年 | 39篇 |
2013年 | 58篇 |
2012年 | 67篇 |
2011年 | 74篇 |
2010年 | 40篇 |
2009年 | 43篇 |
2008年 | 53篇 |
2007年 | 45篇 |
2006年 | 65篇 |
2005年 | 40篇 |
2004年 | 41篇 |
2003年 | 27篇 |
2002年 | 25篇 |
2001年 | 22篇 |
2000年 | 17篇 |
1999年 | 22篇 |
1998年 | 7篇 |
1997年 | 14篇 |
1996年 | 6篇 |
1995年 | 13篇 |
1992年 | 18篇 |
1991年 | 19篇 |
1990年 | 15篇 |
1989年 | 22篇 |
1988年 | 24篇 |
1987年 | 24篇 |
1986年 | 22篇 |
1985年 | 21篇 |
1984年 | 12篇 |
1983年 | 22篇 |
1982年 | 16篇 |
1981年 | 11篇 |
1980年 | 11篇 |
1979年 | 17篇 |
1978年 | 13篇 |
1977年 | 10篇 |
1976年 | 11篇 |
1974年 | 9篇 |
1973年 | 10篇 |
1972年 | 10篇 |
1971年 | 7篇 |
1970年 | 6篇 |
排序方式: 共有1324条查询结果,搜索用时 0 毫秒
111.
112.
Defects in the leptin axis reduce abundance of the ABCG5-ABCG8 sterol transporter in liver 总被引:1,自引:0,他引:1
ABGG5 (G5) and ABCG8 (G8) are ABC half-transporters that dimerize within the endoplasmic reticulum, traffic to the cell surface, and mediate cholesterol excretion into bile. Mice harboring defects in the leptin axis (db/db and ob/ob) have reduced biliary cholesterol concentrations. Rapid weight loss brought about by administration of leptin or dietary restriction increases biliary cholesterol excretion. We hypothesized that the reduction in biliary cholesterol in mice harboring defects in the leptin axis is associated with a reduction in G5G8 transporters and that levels of the transporter would increase with leptin administration and dietary restriction. We examined mRNA and protein levels for G5 and G8 in db/db and ob/ob mice. In both models G5 and G8 protein levels were reduced. In ob/ob mice, both leptin administration and dietary restriction increased G5 and G8 protein and biliary cholesterol concentrations. Finally, we examined the effects of tauroursodeoxycholate, which has been shown to increase biliary cholesterol excretion and function as a molecular chaperone. Tauroursodeoxycholate increased G5 and G8 protein and biliary cholesterol concentrations in both wild-type and db/db mice. Our results indicate that the mechanism for reduced biliary cholesterol excretion in db/db and ob/ob mice involves reductions in G5 and G8 protein levels and that this may occur at the level of G5G8 heterodimer assembly within the endoplasmic reticulum. 相似文献
113.
114.
Dynamics and Biodiversity of Populations of Lactic Acid Bacteria and Acetic Acid Bacteria Involved in Spontaneous Heap Fermentation of Cocoa Beans in Ghana 总被引:3,自引:1,他引:2 下载免费PDF全文
Nicholas Camu Tom De Winter Kristof Verbrugghe Ilse Cleenwerck Peter Vandamme Jemmy S. Takrama Marc Vancanneyt Luc De Vuyst 《Applied microbiology》2007,73(6):1809-1824
The Ghanaian cocoa bean heap fermentation process was studied through a multiphasic approach, encompassing both microbiological and metabolite target analyses. A culture-dependent (plating and incubation, followed by repetitive-sequence-based PCR analyses of picked-up colonies) and culture-independent (denaturing gradient gel electrophoresis [DGGE] of 16S rRNA gene amplicons, PCR-DGGE) approach revealed a limited biodiversity and targeted population dynamics of both lactic acid bacteria (LAB) and acetic acid bacteria (AAB) during fermentation. Four main clusters were identified among the LAB isolated: Lactobacillus plantarum, Lactobacillus fermentum, Leuconostoc pseudomesenteroides, and Enterococcus casseliflavus. Other taxa encompassed, for instance, Weissella. Only four clusters were found among the AAB identified: Acetobacter pasteurianus, Acetobacter syzygii-like bacteria, and two small clusters of Acetobacter tropicalis-like bacteria. Particular strains of L. plantarum, L. fermentum, and A. pasteurianus, originating from the environment, were well adapted to the environmental conditions prevailing during Ghanaian cocoa bean heap fermentation and apparently played a significant role in the cocoa bean fermentation process. Yeasts produced ethanol from sugars, and LAB produced lactic acid, acetic acid, ethanol, and mannitol from sugars and/or citrate. Whereas L. plantarum strains were abundant in the beginning of the fermentation, L. fermentum strains converted fructose into mannitol upon prolonged fermentation. A. pasteurianus grew on ethanol, mannitol, and lactate and converted ethanol into acetic acid. A newly proposed Weissella sp., referred to as “Weissella ghanaensis,” was detected through PCR-DGGE analysis in some of the fermentations and was only occasionally picked up through culture-based isolation. Two new species of Acetobacter were found as well, namely, the species tentatively named “Acetobacter senegalensis” (A. tropicalis-like) and “Acetobacter ghanaensis” (A. syzygii-like). 相似文献
115.
Verlinden L Eelen G Van Hellemont R Engelen K Beullens I Van Camp M Marchal K Mathieu C Bouillon R Verstuyf A 《The Journal of steroid biochemistry and molecular biology》2007,103(3-5):411-415
A previous cDNA microarray analysis in murine MC3T3-E1 osteoblasts revealed a cluster of genes involved in cell cycle progression that was significantly down-regulated after a single treatment with 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] [L. Verlinden, G. Eelen, I. Beullens, M. Van Camp, P. Van Hummelen, K. Engelen, R. Van Hellemont, K. Marchal, B. De Moor, F. Foijer, H. Te Riele, M. Beullens, M. Bollen, C. Mathieu, R. Bouillon, A. Verstuyf, Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes down-regulated by 1,25-dihydroxyvitamin D3, J. Biol. Chem. 280 (45) (2005) 37319-37330]. Among those genes were the DNA replication and DNA damage checkpoint proteins, Chk1 and Claspin, of which the human homologues were recently shown to be E2F-responsive. Quantitative real-time PCR experiments in 1,25(OH)(2)D(3)-treated MC3T3-E1 cells confirmed the down-regulation observed in the microarray experiment. Moreover, Chk1 and Claspin promoter activities were also reduced after incubation with 1,25(OH)(2)D(3), and this reduction was mediated through the E2F recognition motifs within their promoters because mutation of these motifs almost completely abolished the repressive effect of 1,25(OH)(2)D(3). The antiproliferative effect of 1,25(OH)(2)D(3) as well as its potential to down-regulate the expression of Chk1 and Claspin depended on the pocket proteins p107 and p130 because 1,25(OH)(2)D(3) lost its antiproliferative action and failed to repress these E2F-target genes in p107(-/-);p130(-/-)-cells, but not in pRb(-/-)-cells. 相似文献
116.
117.
118.
Kristof Moonens Imke Van den Broeck Maia De Kerpel Francine Deboeck Hanne Raymaekers Han Remaut Henri De Greve 《The Journal of biological chemistry》2015,290(13):8409-8419
Enterotoxigenic Escherichia coli (ETEC) strains are important causes of intestinal disease in humans and lead to severe production losses in animal farming. A range of fimbrial adhesins in ETEC strains determines host and tissue tropism. ETEC strains expressing F4 fimbriae are associated with neonatal and post-weaning diarrhea in piglets. Three naturally occurring variants of F4 fimbriae (F4ab, F4ac, and F4ad) exist that differ in the primary sequence of their major adhesive subunit FaeG, and each features a related yet distinct receptor binding profile. Here the x-ray structure of FaeGad bound to lactose provides the first structural insight into the receptor specificity and mode of binding by the poly-adhesive F4 fimbriae. A small D′-D″-α1-α2 subdomain grafted on the immunoglobulin-like core of FaeG hosts the carbohydrate binding site. Two short amino acid stretches Phe150–Glu152 and Val166–Glu170 of FaeGad bind the terminal galactose in the lactosyl unit and provide affinity and specificity to the interaction. A hemagglutination-based assay with E. coli expressing mutant F4ad fimbriae confirmed the elucidated co-complex structure. Interestingly, the crucial D′-α1 loop that borders the FaeGad binding site adopts a different conformation in the two other FaeG variants and hints at a heterogeneous binding pocket among the FaeG serotypes. 相似文献
119.
Evolution of bilaterally asymmetrical larvae in freshwater mussels (Bivalvia: Unionoida: Unionidae) 下载免费PDF全文
Bilaterally asymmetrical glochidia (i.e. bivalved parasitic larvae bearing a large marginal appendage on a single valve) have been reported from five Asian freshwater mussel genera belonging to two separate subfamilies, the Gonideinae (i.e. Pseudodon, Solenaia, and Physunio) and Rectidentinae (i.e. Contradens and Trapezoideus). This classification requires that the bilaterally asymmetrical glochidium‐bearing mussels are not monophyletic, and suggests that this atypical larval morphology evolved twice in the same geographic region. Although homoplastic glochidium characters are known (e.g. marginal appendages and size), we hypothesized that bilaterally asymmetrical glochidia represent a novel morphological synapomorphy. We tested the monophyly of the mussels bearing bilaterally asymmetrical glochidia using a molecular matrix consisting of representatives from all six freshwater mussel families and three molecular markers (28S, 16S, and COI). Bayesian inference, maximum likelihood, and ancestral state reconstruction were employed to estimate the phylogeny and larval trait transformations. The reconstructed phylogeny rejects the monophyly of the asymmetrical glochidium‐bearing mussels and resolves two putative origins of asymmetrical glochidia; however, ancestral state reconstruction supports asymmetrical glochidia as a synapomorphy of only one supraspecific taxon of the Rectidentinae. In the Gonideinae, asymmetrical glochidia were autapomorphic of Pseudodon cambodjensis (Petit, 1865). That is, no other taxa resolved among the Gonideinae had bilaterally asymmetrical glochidia, including other Pseudodon species. We describe how the alleged intrageneric glochidial variation in Pseudodon, and in the other genera of the Gonideinae reported to have asymmetrical glochidia (i.e. Solenaia and Physunio), challenge the resolved convergence of asymmetrical glochidia. Our results are discussed in the context of freshwater mussel larval evolution, patterns in life‐history traits, and the classification of freshwater mussels generally. © 2015 The Linnean Society of London 相似文献
120.