全文获取类型
收费全文 | 848篇 |
免费 | 82篇 |
出版年
2021年 | 10篇 |
2020年 | 12篇 |
2019年 | 10篇 |
2018年 | 8篇 |
2017年 | 17篇 |
2016年 | 24篇 |
2015年 | 33篇 |
2014年 | 42篇 |
2013年 | 50篇 |
2012年 | 50篇 |
2011年 | 60篇 |
2010年 | 43篇 |
2009年 | 52篇 |
2008年 | 39篇 |
2007年 | 54篇 |
2006年 | 54篇 |
2005年 | 44篇 |
2004年 | 45篇 |
2003年 | 46篇 |
2002年 | 49篇 |
2001年 | 12篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1998年 | 13篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 8篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1964年 | 2篇 |
1956年 | 2篇 |
1937年 | 2篇 |
排序方式: 共有930条查询结果,搜索用时 31 毫秒
41.
In this communication, we describe the isolation of a Lactobacillus delbrueckii subsp. bulgaricus 92063 mutant strain named pH-P11, which differed from the parent strain by low proteolytic activity and altered regulation of expression of lacZ in the presence of glucose or lactose. In the presence of lactose, beta-galactosidase activity was approximately twice as high in pH-P11 than in the wild type. pH-P11 exhibited protosymbiosis together with Streptococcus thermophilus. Yoghurt produced with pH-P11 was characterized by low acidity and little post-acidification during storage. The organoleptic properties (absence of bitterness and other off-flavors, weak sourness, and clear yoghurt taste) were those of a typical "yoghurt mild". This mild flavor was achieved at rather high cell counts of lactobacilli even at the end of shelf-life. High cell counts in conjunction with high beta-galactosidase activity make pH-P11 an interesting strain for application in yoghurt especially designed for consumers with lactose malabsorption. In contrast to "yoghurt mild", which is predominantly produced with Lactobacillus acidophilus together with Streptococcus thermophilus, the product obtained by fermentation with pH-P11 and Streptococcus thermophilus concurs with international standards for yoghurt. During frequent sub-culturing, strain pH-P11, which is supposed to differ from the wild type by one or a few so-far-not-characterized mutations, showed sufficient stability for application in industrial production. 相似文献
42.
43.
Activated liver X receptors stimulate adipocyte differentiation through induction of peroxisome proliferator-activated receptor gamma expression
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Seo JB Moon HM Kim WS Lee YS Jeong HW Yoo EJ Ham J Kang H Park MG Steffensen KR Stulnig TM Gustafsson JA Park SD Kim JB 《Molecular and cellular biology》2004,24(8):3430-3444
Liver X receptors (LXRs) are nuclear hormone receptors that regulate cholesterol and fatty acid metabolism in liver tissue and in macrophages. Although LXR activation enhances lipogenesis, it is not well understood whether LXRs are involved in adipocyte differentiation. Here, we show that LXR activation stimulated the execution of adipogenesis, as determined by lipid droplet accumulation and adipocyte-specific gene expression in vivo and in vitro. In adipocytes, LXR activation with T0901317 primarily enhanced the expression of lipogenic genes such as the ADD1/SREBP1c and FAS genes and substantially increased the expression of the adipocyte-specific genes encoding PPARγ (peroxisome proliferator-activated receptor γ) and aP2. Administration of the LXR agonist T0901317 to lean mice promoted the expression of most lipogenic and adipogenic genes in fat and liver tissues. It is of interest that the PPARγ gene is a novel target gene of LXR, since the PPARγ promoter contains the conserved binding site of LXR and was transactivated by the expression of LXRα. Moreover, activated LXRα exhibited an increase of DNA binding to its target gene promoters, such as ADD1/SREBP1c and PPARγ, which appeared to be closely associated with hyperacetylation of histone H3 in the promoter regions of those genes. Furthermore, the suppression of LXRα by small interfering RNA attenuated adipocyte differentiation. Taken together, these results suggest that LXR plays a role in the execution of adipocyte differentiation by regulation of lipogenesis and adipocyte-specific gene expression. 相似文献
44.
The anaerobic degradation pathways of toluene and m-xylene are initiated by addition of a fumarate cosubstrate to the methyl group of the hydrocarbon, yielding (R)-benzylsuccinate and (3-methylbenzyl)succinate, respectively, as first intermediates. These reactions are catalyzed by a novel glycyl-radical enzyme, (R)-benzylsuccinate synthase. Substrate specificities of benzylsuccinate synthases were analyzed in Azoarcus sp. strain T and Thauera aromatica strain K172. The enzyme of Azoarcus sp. strain T converts toluene, but also all xylene and cresol isomers, to the corresponding succinate adducts, whereas the enzyme of T. aromatica is active with toluene and all cresols, but not with any xylene isomer. This corresponds to the capabilities of Azoarcus sp. strain T to grow on either toluene or m-xylene, and of T. aromatica to grow on toluene as sole hydrocarbon substrate. Thus, differences in the substrate spectra of the respective benzylsuccinate synthases of the two strains contribute to utilization of different aromatic hydrocarbons, although growth on different substrates also depends on additional determinants. We also provide direct evidence by electron paramagnetic resonance (EPR) spectroscopy that glycyl radical enzymes corresponding to substrate-induced benzylsuccinate synthases are specifically detectable in anoxically prepared extracts of toluene- or m-xylene-grown cells. The presence of the EPR signals and the determined amount of the radical are consistent with the respective benzylsuccinate synthase activities. The properties of the EPR signals are highly similar to those of the prototype glycyl radical enzyme pyruvate formate lyase, but differ slightly from previously reported parameters for partially purified benzylsuccinate synthase. 相似文献
45.
Neurotrophin action on a rapid timescale 总被引:6,自引:0,他引:6
Mechanisms underlying the fast action of neurotrophins include intracellular Ca(2+) signaling, neuronal excitation, augmentation of synaptic excitation by modulation of N-methyl-d-aspartate receptor activity and control of synaptic inhibition through the regulation of the K(+)-Cl(-) cotransporter KCC2. The fastest action of brain-derived neurotrophic factor and neurotrophin-4/5 occurs within milliseconds, and involves activation of TrkB and the opening of the Na(+) channel Na(v)1.9. Through these rapid actions, neurotrophins shape neuronal activity, modulate synaptic transmission and produce instructive signals for the induction of long-term changes in the efficacy of synaptic transmission. 相似文献
46.
The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis
下载免费PDF全文
![点击此处可从《PLoS biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
47.
We show in Gram-negative and Gram-positive bacteria the appearance of highly acidic proteins, which are highly phosphorylated. This group of proteins includes many cellular proteins, such as chaperones, biosynthetic, and metabolic enzymes. These proteins accumulate under stress conditions or under conditions, which overload the proteolytic system. Pulse chase experiments using radioactive phosphate indicate that the phosphorylated proteins have a short half-life, suggesting that they could be degradation intermediates. Moreover, results from in vitro experiments in Escherichia coli indicated that ribosomal proteins become susceptible to proteolysis after polyphosphorylation. Therefore, it is possible that the highly phosphorylated proteins represent a group of proteins tagged for degradation by phosphorylation. Such a tagging process may be involved in a general bacterial degradation pathway. 相似文献
48.
Miranda FF Thórólfsson M Teigen K Sanchez-Ruiz JM Martínez A 《Protein science : a publication of the Protein Society》2004,13(5):1219-1226
Phosphorylation of phenylalanine hydroxylase (PAH) at Ser16 by cAMP-dependent protein kinase increases the basal activity of the enzyme and its resistance to tryptic proteolysis. The modeled structures of the full-length phosphorylated and unphosphorylated enzyme were subjected to molecular dynamics simulations, and we analyzed the energy of charge-charge interactions for individual ionizable residues in the final structures. These calculations showed that the conformational changes induced by incorporation of phosphate were localized and limited mostly to the region around the phosphoserine (Arg13-Asp17) and a region around the active site in the catalytic domain that includes residues involved in the binding of the iron and the substrate L-Phe (Arg270 and His285). The absence of a generalized conformational change was confirmed by differential scanning calorimetry, thermal-dependent circular dichroism, fluorescence spectroscopy, and limited chymotryptic proteolysis of the phosphorylated and unphosphorylated PAH. Our results explain the effect of phosphorylation of PAH on both the resistance to proteolysis specifically by trypsin-like enzymes and on the increase in catalytic efficiency. 相似文献
49.
Wiig H Aukland K Tenstad O 《American journal of physiology. Heart and circulatory physiology》2003,284(1):H416-H424
Access to interstitial fluid is of fundamental importance to understand tumor transcapillary fluid balance, including the distribution of probes and therapeutic agents. Tumors were induced by gavage of 9,10-dimethyl-1,2-benzanthracene to rats, and fluid was isolated after anesthesia by exposing tissue to consecutive centrifugations from 27 to 6,800 g. The observed (51)Cr-EDTA (extracellular tracer) tissue fluid-to-plasma ratio obtained from whole tumor or from superficial tumor tissue by centrifugation at 27-424 g was not significantly different from 1.0 (0.92-0.99), suggesting an extracellular origin only. However, fluid collected from excised central tumor parts had a significantly lower ratio (0.66-0.77) for all imposed G forces, suggesting dilution by fluid deriving from a space unavailable for (51)Cr-EDTA. The colloid osmotic pressure in tumor fluid was generally higher than in fluid isolated from the subcutis, attributable to less selective capillaries and impaired lymphatic drainage in tumors. HPLC analysis of tumor fluid showed that low-molecular-weight macromolecules not present in arterial plasma were present in tumor fluid obtained by centrifugation and in venous blood draining the tumor, most likely representing proteins derived from tumor cells. We conclude that low-speed centrifugation may be a simple and reliable method to isolate interstitial fluid from tumors. 相似文献