全文获取类型
收费全文 | 925篇 |
免费 | 65篇 |
出版年
2022年 | 8篇 |
2021年 | 15篇 |
2020年 | 9篇 |
2019年 | 6篇 |
2018年 | 17篇 |
2017年 | 7篇 |
2016年 | 24篇 |
2015年 | 38篇 |
2014年 | 49篇 |
2013年 | 51篇 |
2012年 | 68篇 |
2011年 | 70篇 |
2010年 | 39篇 |
2009年 | 27篇 |
2008年 | 57篇 |
2007年 | 50篇 |
2006年 | 43篇 |
2005年 | 57篇 |
2004年 | 36篇 |
2003年 | 44篇 |
2002年 | 55篇 |
2001年 | 17篇 |
2000年 | 9篇 |
1999年 | 10篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 5篇 |
1994年 | 13篇 |
1993年 | 8篇 |
1992年 | 14篇 |
1991年 | 4篇 |
1990年 | 9篇 |
1989年 | 4篇 |
1988年 | 14篇 |
1987年 | 4篇 |
1986年 | 8篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 7篇 |
1974年 | 3篇 |
1971年 | 5篇 |
1970年 | 3篇 |
排序方式: 共有990条查询结果,搜索用时 15 毫秒
151.
152.
Vikstedt R Metso J Hakala J Olkkonen VM Ehnholm C Jauhiainen M 《Biochemistry》2007,46(42):11979-11986
Phospholipid transfer protein (PLTP) is expressed by macrophage-derived foam cells in human atherosclerotic lesions, suggesting a regulatory role for PLTP in cellular cholesterol homeostasis. However, the exact role of PLTP in the reverse cholesterol transport pathway is not known. PLTP is present in plasma as two forms, a highly active (HA-PLTP) and a lowly active (LA-PLTP) form. In this study we clarify the role of the two forms of PLTP in cholesterol efflux from [3H]cholesterol oleate-acetyl-LDL-loaded THP-1 macrophages. Incubation of HDL in the presence of HA-PLTP resulted in the formation of two types of acceptor particles, prebeta-HDL and large fused HDL. HA-PLTP increased prebeta-HDL formation and caused a 42% increase in [3H]cholesterol efflux to HDL, while LA-PLTP neither formed prebeta-HDL nor increased cholesterol efflux. Removal of the formed prebeta-HDL by immunoprecipitation decreased cholesterol efflux by 47%. Neither HA- nor LA-PLTP enhanced cholesterol efflux to lipid-free apoA-I. Importantly, also the large fused HDL particles formed during incubation of HDL with HA-PLTP acted as efficient cholesterol acceptors. These observations demonstrate that only HA-PLTP increases macrophage cholesterol efflux, via formation of efficient cholesterol acceptors, prebeta-HDL and large fused HDL particles. 相似文献
153.
154.
155.
Katariina Sivenius Leo Niskanen Markku Laakso Matti Uusitupa 《Obesity (Silver Spring, Md.)》2003,11(8):962-970
Objective: We investigated the impact of a three‐amino acid deletion (12Glu9) polymorphism in the α2B‐adrenergic receptor gene on autonomic nervous function. The short form (Glu9/Glu9) of the polymorphism has previously been associated with a reduced basal metabolic rate in obese subjects. Because autonomic nervous function participates in the regulation of energy metabolism, there could be a link between this polymorphism and autonomic nervous function. Research Methods and Procedures: Data of a 10‐year follow‐up study with 126 nondiabetic control subjects and 84 type 2 diabetic patients were used to determine the effects of the 12Glu9 polymorphism on autonomic nervous function. A deep breathing test and an orthostatic test were used to investigate parasympathetic and sympathetic autonomic nervous function. In addition, cardiovascular autonomic function was studied using power spectral analysis of heart rate variability. Results: No significant differences were found in the frequency of the 12Glu9 deletion polymorphism between nondiabetic and diabetic subjects. The nondiabetic men with the Glu9/Glu9 genotype, especially those with abdominal obesity, had significantly lower total and low‐frequency power values in the power spectral analysis when compared with other men. Furthermore, in a longitudinal analysis of 10 years, the decrease in parasympathetic function was greater in nondiabetic men with the Glu9/Glu9 genotype than in the men with the Glu9/Glu12 or Glu12/Glu12 genotypes. Discussion: The results of the present study suggest that the 12Glu9 polymorphism of the α2B‐adrenergic receptor gene modulates autonomic nervous function in Finnish nondiabetic men. In the nondiabetic men with the Glu9/Glu9 genotype, the general autonomic tone is depressed, and vagal activity especially becomes impaired with time. Furthermore, this association is accentuated by central obesity. 相似文献
156.
Maximilian N. Kopylovich Vadim Yu. Kukushkin Matti Haukka 《Inorganica chimica acta》2009,362(9):2994-2998
The reaction between Zn(OAc)2 · 2H2O (1) and the 3-iminoisoindolin-1-ones H2NCNC(O)C6R1R2R3R4 (R1-R4 = H 2; R1, R4 = H, R2, R3 = Cl 3; R1, R3, R4 = H, R2 = Me 4) in EtCN at 70 °C for ca. 12 h affords the novel family of complexes [Zn{H2NCNC(O)C6R1R2R3R4}2(OAc)2] (R1-R4 = H 5; R1, R4 = H, R2, R3 = Cl 6; R1, R3, R4 = H, R2 = Me 7) in excellent (90% and 93% for 5 and 6, correspondingly) to good (64% for 7) yields. The isolated compounds were characterized by elemental analyses (C, H, N), IR, NMR and ESI+-MS. X-ray diffraction data for 2 and 5 indicate that both free (2) and ligated (5) 3-iminoisoindolin-1-ones exist in the zwitterionic form. 相似文献
157.
David P. Fewer Jouni Jokela Leo Rouhiainen Matti Wahlsten Kerttu Koskenniemi Lucas J. Stal Kaarina Sivonen 《Molecular microbiology》2009,73(5):924-937
Nodularia spumigena is a filamentous nitrogen-fixing cyanobacterium that forms toxic blooms in brackish water bodies worldwide. Spumigins are serine protease inhibitors reported from a single strain of N. spumigena isolated from the Baltic Sea. These linear tetrapeptides contain non-proteinogenic amino acids including a C-terminal alcohol derivative of arginine. However, very little is known about these compounds despite the ecological importance of N. spumigena . We show that spumigins are assembled by two non-ribosomal peptide synthetases encoded in a 21 kb biosynthetic gene cluster. The compact non-ribosomal peptide synthetase features a reductive loading and release mechanism. Our analyses demonstrate that the bulk of spumigins produced by N. spumigena are released as peptide aldehydes in contrast to earlier findings. The main spumigin E variant contains an argininal residue and is a potent trypsin inhibitor. Spumigins were present in all of the N. spumigena strains isolated from the Baltic Sea and comprised up to 1% of the dry weight of the cyanobacterium. Our results demonstrate that bloom-forming N. spumigena strains produce a cocktail of enzyme inhibitors, which may explain in part the ecological success of this cyanobacterium in brackish water bodies worldwide. 相似文献
158.
Early succession of bacterial biofilms in paper machines 总被引:1,自引:0,他引:1
Marja Tiirola Tomi Lahtinen Matti Vuento Christian Oker-Blom 《Journal of industrial microbiology & biotechnology》2009,36(7):929-937
Formation of biofilms causes severe problems in paper machines, and hence financial costs. It would be preferable to prevent
attachment of the primary-colonizing bacteria than to control the growth of secondary communities, which are sheltered by
exopolysaccharide slime layers. We have therefore investigated the early succession of paper-machine biofilms by incubating
stainless-steel test coupons in the process water-flow lines in two paper machines operating in slightly alkaline conditions
in temperatures (45 and 49°C) supporting thermophilic microbes. Microbial succession was profiled using length heterogeneity
analysis of PCR-amplified 16S rRNA genes (LH-PCR) and linking the sequence data of the created 16S rRNA gene libraries to
the dominant LH-PCR peaks. Although the bacterial fingerprints obtained from the attached surface communities varied slightly
in different samples, the biomarker signals of the dominating primary-colonizing bacterial groups remained high over time
in each paper machine. Most of the 16S rRNA gene copies in the early biofilms were assigned to the genera Rhodobacter, Tepidimonas, and Cloacibacterium. The dominance of these sequence types decreased in the developing biofilms. Finally, as phylogenetically identical primary-colonizers
were detected in the two different paper mills, the machines evidently had similar environmental conditions for bacterial
growth and potentially a common source of contamination. 相似文献
159.
The Closest Relatives of Icosahedral Viruses of Thermophilic Bacteria Are among Viruses and Plasmids of the Halophilic Archaea
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Matti Jalasvuori Silja T. Jaatinen Simonas Laurinavi?ius Elina Ahola-Iivarinen Nisse Kalkkinen Dennis H. Bamford Jaana K. H. Bamford 《Journal of virology》2009,83(18):9388-9397
We have sequenced the genome and identified the structural proteins and lipids of the novel membrane-containing, icosahedral virus P23-77 of Thermus thermophilus. P23-77 has an ∼17-kb circular double-stranded DNA genome, which was annotated to contain 37 putative genes. Virions were subjected to dissociation analysis, and five protein species were shown to associate with the internal viral membrane, while three were constituents of the protein capsid. Analysis of the bacteriophage genome revealed it to be evolutionarily related to another Thermus phage (IN93), archaeal Halobacterium plasmid (pHH205), a genetic element integrated into Haloarcula genome (designated here as IHP for integrated Haloarcula provirus), and the Haloarcula virus SH1. These genetic elements share two major capsid proteins and a putative packaging ATPase. The ATPase is similar with the ATPases found in the PRD1-type viruses, thus providing an evolutionary link to these viruses and furthering our knowledge on the origin of viruses.Three-dimensional structures of the major capsid proteins, as well as the architecture of the virion and the sequence similarity of putative genome packaging ATPases, have revealed unexpected evolutionary connection between virus families. Viruses infecting hosts residing in different domains of life (Bacteria, Archaea, and Eukarya) share common structural elements and possibly also ways to package the viral genome (8, 13, 41). It has been proposed that the set of genes responsible for virion assembly is a hallmark of the virus and is designated as the innate viral “self,” which may retain its identity through evolutionary times (5). Based on this, it is proposed that viruses can be classified into lineages that span the different domains of life. Therefore, the studies of new virus isolates might provide insights into the events that led to the origin of viruses and maybe even the origin of life itself (34, 40). However, viruses are known to be genetic mosaics (28), and these structural lineages therefore do not reflect the evolutionary history of all genes in a given virus. For example, the genome replication strategies vary significantly even in the currently established lineages (41) and, consequently, a structural approach does not point out to a specific form of replication in the ancestor. Nevertheless, as the proposal for a viral self is driven from information on viral structures and pathways of genome encapsidation, the ancestral form of the self was likely to be composed of a protective coat and the necessary mechanisms to incorporate the genetic material within the coat.Viruses structurally related to bacteriophage PRD1, a phage infecting gram-negative bacteria, have been identified in all three domains of life, and the lineage hypothesis was first proposed based on structural information on such viruses. Initially, PRD1 and human adenovirus were proposed to originate from a common ancestor mainly due to the same capsid organization (T=25) and the major coat protein topology, the trimeric double β-barrel fold (12). In addition, these viruses share a common vertex organization and replication mechanism (20, 31, 53, 63). PRD1 is an icosahedral virus with an inner membrane, whereas adenovirus lacks the membrane. Later, many viruses with similar double β-barrel fold in the major coat protein have been discovered and included to this viral lineage. For example, the fold is present in Paramecium bursaria Chlorella virus 1 (56) of algae, Bam35 (45) of gram-positive bacteria, PM2 (2) of gram-negative marine bacteria, and Sulfolobus turreted icosahedral virus (STIV) (38) of an archaeal host. Moreover, genomic analyses have revealed a common set of genes in a number of nucleocytoplasmic large DNA viruses. Chilo iridescent virus and African swine fever virus 1 are related to Paramecium bursaria Chlorella virus 1 and most probably share structural similarity to PRD1-type viruses (13, 30, 31, 68). The largest known viruses, represented by mimivirus and poxvirus, may also belong to this lineage (29, 77). Two euryarchaeal proviruses, TKV4 and MVV, are also proposed to belong to this lineage based on bioinformatic searches (42). The proposed PRD1-related viruses share the same basic architectural principles despite major differences in the host organisms and particle and genome sizes (1, 2, 38, 56). PM2, for example, has a genome of only 10 kbp, whereas mimivirus (infecting Acanthamoeba polyphaga) double-stranded DNA (dsDNA) genome is 1.2 Mbp in size (59).How many virion structure-based lineages might there be? This obviously relates to the number of protein folds that have the properties needed to make viral capsids. It has been noted that, in addition to PRD1-type viruses, at least tailed bacterial and archaeal viruses, as well as herpesviruses, share the same coat protein fold. Also, certain dsRNA viruses seem to have structural and functional similarities, although their hosts include bacteria and yeasts, as well as plants and animals (6, 18, 19, 27, 55, 60, 74). Obviously, many structural principles to build a virus capsid exist, and it has been suggested that especially geothermally heated environments have preserved many of the anciently formed virus morphotypes (35).Thermophilic dsDNA bacteriophage P23-77 was isolated from an alkaline hot spring in New Zealand on Thermus thermophilus (17) ATCC 33923 (deposited as Thermus flavus). P23-77 was shown to have an icosahedral capsid and possibly an internal membrane but no tail (81). Previously, another Thermus virus, IN93, with a similar morphology has been described (50). IN93 was inducible from a lysogenic strain of Thermus aquaticus TZ2, which was isolated from hot spring soil in Japan. Recently, P23-77 was characterized in more detail (33). It has an icosahedral protein coat, organized in a T=28 capsid lattice (21). The presence of an internal membrane was confirmed, and lipids were shown to be constituents of the virion. Ten structural proteins were identified, with apparent molecular masses ranging from 8 to 35 kDa. Two major protein species with molecular masses of 20 and 35 kDa were proposed to make the capsomers, one forming the hexagonal building blocks and the other the two towers that decorate the capsomer bases (33). Surprisingly, P23-77 is structurally closest to the haloarchaeal virus SH1, which is the only other example of a T=28 virion architecture (32, 33). In both cases it was proposed that the capsomers are made of six single β-barrels opposing the situation with the other structurally related viruses where the hexagonal capsomers are made of three double β-barrel coat protein monomers (8).In the present study we analyze the dsDNA genome of P23-77. Viral membrane proteins and those associated with the capsid were identified by virion dissociation studies. The protein chemistry data and genome annotation are consistent with the results of the disruption studies. A detailed analysis of the lipid composition of P23-77 and its T. thermophilus host was carried out. The data collected here reveal additional challenges in attempts to generate viral lineages based on the structural and architectural properties of the virion. 相似文献
160.
Matti Uusitupa Markku Peltonen Jaana Lindstr?m Sirkka Aunola Pirjo Ilanne-Parikka Sirkka Kein?nen-Kiukaanniemi Timo T. Valle Johan G. Eriksson Jaakko Tuomilehto for the Finnish Diabetes Prevention Study Group 《PloS one》2009,4(5)