全文获取类型
收费全文 | 2700篇 |
免费 | 248篇 |
国内免费 | 1篇 |
出版年
2024年 | 4篇 |
2023年 | 18篇 |
2022年 | 12篇 |
2021年 | 64篇 |
2020年 | 46篇 |
2019年 | 39篇 |
2018年 | 59篇 |
2017年 | 60篇 |
2016年 | 95篇 |
2015年 | 154篇 |
2014年 | 148篇 |
2013年 | 182篇 |
2012年 | 260篇 |
2011年 | 253篇 |
2010年 | 145篇 |
2009年 | 134篇 |
2008年 | 183篇 |
2007年 | 154篇 |
2006年 | 168篇 |
2005年 | 171篇 |
2004年 | 131篇 |
2003年 | 113篇 |
2002年 | 110篇 |
2001年 | 20篇 |
2000年 | 12篇 |
1999年 | 32篇 |
1998年 | 18篇 |
1997年 | 9篇 |
1996年 | 13篇 |
1995年 | 12篇 |
1994年 | 11篇 |
1993年 | 4篇 |
1992年 | 14篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1981年 | 3篇 |
1977年 | 3篇 |
1973年 | 3篇 |
1971年 | 5篇 |
1969年 | 3篇 |
1967年 | 4篇 |
1965年 | 4篇 |
1878年 | 2篇 |
排序方式: 共有2949条查询结果,搜索用时 323 毫秒
101.
Low concentrations of branched-chain fatty acids, such as isobutyric and isovaleric acids, develop during the ripening of hard cheeses and contribute to the beneficial flavor profile. Catabolism of amino acids, such as branched-chain amino acids, by bacteria via aminotransferase reactions and alpha-keto acids is one mechanism to generate these flavorful compounds; however, metabolism of alpha-keto acids to flavor-associated compounds is controversial. The objective of this study was to determine the ability of Brevibacterium linens BL2 to produce fatty acids from amino acids and alpha-keto acids and determine the occurrence of the likely genes in the draft genome sequence. BL2 catabolized amino acids to fatty acids only under carbohydrate starvation conditions. The primary fatty acid end products from leucine were isovaleric acid, acetic acid, and propionic acid. In contrast, logarithmic-phase cells of BL2 produced fatty acids from alpha-keto acids only. BL2 also converted alpha-keto acids to branched-chain fatty acids after carbohydrate starvation was achieved. At least 100 genes are potentially involved in five different metabolic pathways. The genome of B. linens ATCC 9174 contained these genes for production and degradation of fatty acids. These data indicate that brevibacteria have the ability to produce fatty acids from amino and alpha-keto acids and that carbon metabolism is important in regulating this event. 相似文献
102.
Spike BT Dirlam A Dibling BC Marvin J Williams BO Jacks T Macleod KF 《The EMBO journal》2004,23(21):4319-4329
The retinoblastoma tumor suppressor gene plays important roles in cell cycle control, differentiation and survival during development and is functionally inactivated in most human cancers. Early studies using gene targeting in mice suggested a critical role for pRb in erythropoiesis, while more recent experiments have suggested that many of the abnormal embryonic phenotypes in the Rb null mouse result from a defective placenta. To address this controversy and determine whether Rb has cell intrinsic functions in erythropoiesis, we examined the effects of Rb loss on red cell production following acute deletion of pRb in vitro and under different stress conditions in vivo. Under stress conditions, pRb was required to regulate erythroblast expansion and promote red cell enucleation. Acute deletion of Rb in vitro induced erythroid cell cycle and differentiation defects similar to those observed in vivo. These results demonstrate a cell intrinsic role for pRb in stress erythropoiesis and hematopoietic homeostasis that has relevance for human diseases. 相似文献
103.
Exploiting dendritic cells for cancer immunotherapy: genetic modification of dendritic cells 总被引:5,自引:0,他引:5
Dendritic cells (DCs) are pivotal regulators of immune reactivity and immune tolerance. The observation that DCs can recruit naive T cells has invigorated cancer immunology and led to the proposal of DCs as the basis for vaccines designed for the treatment of cancer. Designing effective strategies to load DCs with antigens is a challenging field of research. The successful realization of gene transfer to DCs will be highly dependent on the employed vector system. Here, we review various viral and non-viral gene transfer systems, and discuss their distinct characteristics and possible advantages and disadvantages in respect to their use in DC-based immunotherapy. 相似文献
104.
Without a doubt, rodent models have been instrumental in describing pathways that lead to pancreatic beta-cell destruction, evaluating potential causes of type 1 diabetes and providing proof-of-principle for the potential of immune-based interventions. However, despite more than two decades of productive research, we are still yet to define an initiating autoantigen for the human disease, to determine the precise mechanisms of beta-cell destruction in humans and to design interventions that prevent or cure type 1 diabetes. In this Perspective article, we propose that a major philosophical change would benefit this field, a proposition that is based on evaluation of situations in which rodent models have provided useful guidance and in which they have led to disappointments. 相似文献
105.
For lintners with negligible amylose retrogradation, crystallinity related inversely to starch amylose content and, irrespective of starch source, incomplete removal of amorphous material was shown. The latter was more pronounced for B-type than for A-type starches. The two predominant lintner populations, with modal degrees of polymerization (DP) of 13-15 and 23-27, were best resolved for amylose-deficient and A-type starches. Results indicate a more specific hydrolysis of amorphous lamellae in such starches. Small-angle X-ray scattering showed a more intense 9-nm scattering peak for native amylose-deficient A-type starches than for their regular or B-type analogues. The experimental evidence indicates a lower contrasting density within the "crystalline" shells of the latter starches. A higher density in the amorphous lamellae, envisaged by the lamellar helical model, explains the relative acid resistance of linear amylopectin chains with DP > 20, observed in lintners of B-type starches. Because amylopectin chain length distributions were similar for regular and amylose-deficient starches of the same crystal type, we deduce that the more dense (and ordered) packing of double helices into lamellar structures in amylose-deficient starches is due to a different amylopectin branching pattern. 相似文献
106.
Machczynski MC Vijgenboom E Samyn B Canters GW 《Protein science : a publication of the Protein Society》2004,13(9):2388-2397
Laccases and other four-copper oxidases are usually constructed of three domains: Domains one and three house the copper sites, and the second domain often helps form a substrate-binding cleft. In contrast to this arrangement, the genome of Streptomyces coelicolor was found to encode a small, four-copper oxidase that lacks the second domain. This protein is representative of a new family of enzymes--the two-domain laccases. Disruption of the corresponding gene abrogates laccase activity in the growth media. We have recombinantly expressed this enzyme, called SLAC, in Escherichia coli and characterized it. The enzyme binds four copper ions/monomer, and UV-visible absorption and EPR measurements confirm that the conserved type 1 copper site and trinuclear cluster are intact. We also report the first known paramagnetic NMR spectrum for the trinuclear copper cluster of a protein from the laccase family. The enzyme is highly stable, retaining activity as a dimer in denaturing gels after boiling and SDS treatment. The activity of the enzyme against 2,6-dimethoxyphenol (DMP) peaks at an unprecedentedly high pH (9.4), whereas the activity against ferrocyanide decreases with pH. SLAC binds negatively charged substrates more tightly than positively charged or uncharged molecules. 相似文献
107.
Phosphatidylinositol 4-kinasebeta is critical for functional association of rab11 with the Golgi complex 下载免费PDF全文
de Graaf P Zwart WT van Dijken RA Deneka M Schulz TK Geijsen N Coffer PJ Gadella BM Verkleij AJ van der Sluijs P van Bergen en Henegouwen PM 《Molecular biology of the cell》2004,15(4):2038-2047
Phosphatidylinositol 4-kinasebeta (PI4Kbeta) plays an essential role in maintaining the structural integrity of the Golgi complex. In a search for PI4Kbeta-interacting proteins, we found that PI4Kbeta specifically interacts with the GTP-bound form of the small GTPase rab11. The PI4Kbeta-rab11 interaction is of functional significance because inhibition of rab11 binding to PI4Kbeta abolished the localization of rab11 to the Golgi complex and significantly inhibited transport of vesicular stomatitis virus G protein from the Golgi complex to the plasma membrane. We propose that a novel function of PI4Kbeta is to act as a docking protein for rab11 in the Golgi complex, which is important for biosynthetic membrane transport from the Golgi complex to the plasma membrane. 相似文献
108.
Haagmans BL Kuiken T Martina BE Fouchier RA Rimmelzwaan GF van Amerongen G van Riel D de Jong T Itamura S Chan KH Tashiro M Osterhaus AD 《Nature medicine》2004,10(3):290-293
The primary cause of severe acute respiratory syndrome (SARS) is a newly discovered coronavirus. Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage. Lack of understanding of the pathogenesis of SARS has prevented the rational development of a therapy against this disease. Here we show extensive SCV antigen expression in type 1 pneumocytes of experimentally infected cynomolgus macaques (Macaca fascicularis) at 4 d postinfection (d.p.i.), indicating that this cell type is the primary target for SCV infection early in the disease, and explaining the subsequent pulmonary damage. We also show that prophylactic treatment of SCV-infected macaques with the antiviral agent pegylated interferon-alpha (IFN-alpha) significantly reduces viral replication and excretion, viral antigen expression by type 1 pneumocytes and pulmonary damage, compared with untreated macaques. Postexposure treatment with pegylated IFN-alpha yielded intermediate results. We therefore suggest that pegylated IFN-alpha protects type 1 pneumocytes from SCV infection, and should be considered a candidate drug for SARS therapy. 相似文献
109.
Plumage colour in nestling blue tits: sexual dichromatism,condition dependence and genetic effects 总被引:15,自引:0,他引:15
Johnsen A Delhey K Andersson S Kempenaers B 《Proceedings. Biological sciences / The Royal Society》2003,270(1521):1263-1270
Sexual-selection theory assumes that there are costs associated with ornamental plumage coloration. While pigment-based ornaments have repeatedly been shown to be condition dependent, this has been more difficult to demonstrate for structural colours. We present evidence for condition dependence of both types of plumage colour in nestling blue tits (Parus caeruleus). Using reflectance spectrometry, we show that blue tit nestlings are sexually dichromatic, with males having more chromatic (more 'saturated') and ultraviolet (UV)-shifted tail coloration and more chromatic yellow breast coloration. The sexual dimorphism in nestling tail coloration is qualitatively similar to that of chick-feeding adults from the same population. By contrast, the breast plumage of adult birds is not sexually dichromatic in terms of chroma. In nestlings, the chroma of both tail and breast feathers is positively associated with condition (body mass on day 14). The UV/blue hue of the tail feathers is influenced by paternally inherited genes, as indicated by a maternal half-sibling comparison. We conclude that the expression of both carotenoid-based and structural coloration seems to be condition dependent in blue tit nestlings, and that there are additional genetic effects on the hue of the UV/blue tail feathers. The signalling or other functions of sexual dichromatism in nestlings remain obscure. Our study shows that nestling blue tits are suitable model organisms for the study of ontogenetic costs and heritability of both carotenoid-based and structural colour in birds. 相似文献
110.
Delhey K Johnsen A Peters A Andersson S Kempenaers B 《Proceedings. Biological sciences / The Royal Society》2003,270(1528):2057-2063
In socially monogamous species, extra-pair paternity can increase the variance in reproductive success and thereby the potential for sexual selection on male ornaments. We studied whether male secondary sexual ornaments are selected through within- and/or extra-pair reproductive success in the blue tit (Parus caeruleus). Male blue tits display a bright blue crown plumage, which reflects substantially in the ultraviolet (UV) and previously has been indicated to be an important sexual signal. We show that males with a more UV-shifted crown hue were less cuckolded, which probably resulted from female preference for more ornamented mates. By contrast, however, older males and males with a less UV-shifted hue sired more extra-pair young. This probably did not reflect direct female preference, since cuckolders were not less UV-ornamented than the males they cuckolded. Alternatively, a trade-off between UV ornamentation and other traits that enhance extra-pair success could explain this pattern. Our results might reflect two alternative male mating tactics, where more UV-ornamented males maximize within-pair success and less UV-ornamented males maximize extra-pair success. Since crown colour was selected in opposite directions by within-pair and extra-pair paternity, directional selection through extra-pair matings seemed weak, at least in this population and breeding season. Reduced intensity of sexual selection due to alternative mating tactics constitutes a potential mechanism maintaining additive genetic variance of male ornaments. 相似文献