全文获取类型
收费全文 | 496篇 |
免费 | 52篇 |
国内免费 | 1篇 |
专业分类
549篇 |
出版年
2022年 | 3篇 |
2021年 | 8篇 |
2019年 | 6篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 23篇 |
2014年 | 20篇 |
2013年 | 29篇 |
2012年 | 32篇 |
2011年 | 30篇 |
2010年 | 17篇 |
2009年 | 19篇 |
2008年 | 14篇 |
2007年 | 24篇 |
2006年 | 18篇 |
2005年 | 24篇 |
2004年 | 22篇 |
2003年 | 18篇 |
2002年 | 13篇 |
2001年 | 10篇 |
2000年 | 18篇 |
1999年 | 14篇 |
1998年 | 15篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1989年 | 13篇 |
1988年 | 12篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1976年 | 2篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 2篇 |
1971年 | 7篇 |
1928年 | 4篇 |
1920年 | 2篇 |
排序方式: 共有549条查询结果,搜索用时 15 毫秒
91.
Humphreys MJ Moon RP Klinder A Fowler SD Rupp K Bur D Ridley RG Berry C 《FEBS letters》1999,463(1-2):43-48
The gene encoding an aspartic proteinase precursor (proplasmepsin) from the rodent malaria parasite Plasmodium berghei has been cloned. Recombinant P. berghei plasmepsin hydrolysed a synthetic peptide substrate and this cleavage was prevented by the general aspartic proteinase inhibitor, isovaleryl pepstatin and by Ro40-4388, a lead compound for the inhibition of plasmepsins from the human malaria parasite Plasmodium falciparum. Southern blotting detected only one proplasmepsin gene in P. berghei. Two plasmepsins have previously been reported in P. falciparum. Here, we describe two further proplasmepsin genes from this species. The suitability of P. berghei as a model for the in vivo evaluation of plasmepsin inhibitors is discussed. 相似文献
92.
The Chlamydia pneumoniae bacteriophage was first identified in isolate AR-39. Its relevance for chlamydial biology and pathogenicity remains unknown. In this study, a collection of 36 C. pneumoniae isolates was screened and the phage was detected in eight. As the positive isolates differed by several polymorphisms, they presumably belonged to different genetic lineages. It was investigated whether different genotypes of the phage also existed and whether they could be assigned to chlamydial genotypes as evidence of coevolution. Sequencing of >3000 bp of the 4524 bp phage genome revealed complete identity to the published sequences. Thus, it was hypothesized that the genetic conservation was related to easy transmissibility of the phage between C. pneumoniae isolates. Cocultivation of phage positive and negative isolates followed by cloning and identification of different C. pneumoniae genotypes demonstrated for the first time transmissibility of the bacteriophage from one isolate to the other. These observations indicate that the phage is capable of infecting C. pneumoniae isolates of different genetic backgrounds and suggest that all C. pneumoniae strains might be susceptible. The successful in vitro infection of C. pneumoniae with the phage provides the basis for studying its pathogenetic relevance in isolates of identical genetic background and provides a potential tool for genetic manipulation of C. pneumoniae. 相似文献
93.
Frederico?Pieruccini-Faria Kaylena?A?Ehgoetz Martens Carolina?RA?Silveira Jeffery?A?Jones Quincy?J?AlmeidaEmail author 《BMC neurology》2014,14(1):250
Background
Recent research has argued that removal of relevant sensory information during the planning and control of simple, self-paced walking can result in increased demand on central processing resources in Parkinson’s disease (PD). However, little is known about more complex gait tasks that require planning of gait adaptations to cross over an obstacle in PD.Methods
In order to understand the interaction between availability of visual information relevant for self-motion and cognitive load, the current study evaluated PD participants and healthy controls while walking toward and stepping over an obstacle in three visual feedback conditions: (i) no visual restrictions; (ii) vision of the obstacle and their lower limbs while in complete darkness; (iii) vision of the obstacle only while in complete darkness; as well as two conditions including a cognitive load (with a dual task versus without a dual task). Each walk trial was divided into an early and late phase to examine changes associated with planning of step adjustments when approaching the obstacle.Results
Interactions between visual feedback and dual task conditions during the obstacle approach were not significant. Patients with PD had greater deceleration and step time variability in the late phase of the obstacle approach phase while walking in both dark conditions compared to control participants. Additionally, participants with PD had a greater number of obstacle contacts when vision of their lower limbs was not available specifically during the dual task condition. Dual task performance was worse in PD compared to healthy control participants, but notably only while walking in the dark regardless of visual feedback.Conclusions
These results suggest that reducing visual feedback while approaching an obstacle shifts processing to somatosensory feedback to guide movement which imposes a greater demand on planning resources. These results are key to fully understanding why trips and falls occur in those with PD.94.
Candida albicans Sun41p, a putative glycosidase, is involved in morphogenesis, cell wall biogenesis, and biofilm formation 下载免费PDF全文
The SUN gene family has been defined in Saccharomyces cerevisiae and comprises a fungus-specific family of proteins which show high similarity in their C-terminal domains. Genes of this family are involved in different cellular processes, like DNA replication, aging, mitochondrial biogenesis, and cytokinesis. In Candida albicans the SUN family comprises two genes, SUN41 and SIM1. We demonstrate that C. albicans mutants lacking SUN41 show similar defects as found for S. cerevisiae, including defects in cytokinesis. In addition, the SUN41 mutant showed a higher sensitivity towards the cell wall-disturbing agent Congo red, whereas no difference was observed in the presence of calcofluor white. Compared to the wild type, SUN41 deletion strains exhibited a defect in biofilm formation, a reduced adherence on a Caco-2 cell monolayer, and were unable to form hyphae on solid medium under the conditions tested. Interestingly, Sun41p was found to be secreted in the medium of cells growing as blastospores as well as those forming hyphae. Our results support a function of SUN41p as a glycosidase involved in cytokinesis, cell wall biogenesis, adhesion to host tissue, and biofilm formation, indicating an important role in the host-pathogen interaction. 相似文献
95.
华南丘陵地区农林复合生态系统晚稻田甲烷和氧化亚氮排放 总被引:5,自引:0,他引:5
采用静态箱-气相色谱法对晚稻田甲烷(CH4)和氧化亚氮(N2O)排放进行田间原位测定。结果表明,有植株参与的稻田CH4排放通量季节变化与地下5cm温度呈显著正相关关系。稻田CH4和N2O季节平均排放通量在有植株参与时分别为1.16±0.38mgm-2h-1和42.33±20.00μgm-2h-1,而无植株参与的分别为0.15±0.11mgm-2h-1和51.69±15.87μgm-2h-1。水稻种植对CH4的排放影响较大,对N2O的排放影响较小,有植株参与的稻田CH4平均排放量显著高于无植株参与的稻田,N2O的平均排放量无显著差异。 相似文献
96.
MARIA JOSÉ ASINS IRENE VILLALTA MOHAMED M. ALY RAQUEL OLÍAS PAZ ÁLVAREZ DE MORALES RAÚL HUERTAS JUN LI NOELIA JAIME‐PÉREZ ROSARIO HARO VERÓNICA RAGA EMILIO A. CARBONELL ANDRÉS BELVER 《Plant, cell & environment》2013,36(6):1171-1191
The location of major quantitative trait loci (QTL) contributing to stem and leaf [Na+] and [K+] was previously reported in chromosome 7 using two connected populations of recombinant inbred lines (RILs) of tomato. HKT1;1 and HKT1;2, two tomato Na+‐selective class I‐HKT transporters, were found to be closely linked, where the maximum logarithm of odds (LOD) score for these QTLs located. When a chromosome 7 linkage map based on 278 single‐nucleotide polymorphisms (SNPs) was used, the maximum LOD score position was only 35 kb from HKT1;1 and HKT1;2. Their expression patterns and phenotypic effects were further investigated in two near‐isogenic lines (NILs): 157‐14 (double homozygote for the cheesmaniae alleles) and 157‐17 (double homozygote for the lycopersicum alleles). The expression pattern for the HKT1;1 and HKT1;2 alleles was complex, possibly because of differences in their promoter sequences. High salinity had very little effect on root dry and fresh weight and consequently on the plant dry weight of NIL 157‐14 in comparison with 157‐17. A significant difference between NILs was also found for [K+] and the [Na+]/[K+] ratio in leaf and stem but not for [Na+] arising a disagreement with the corresponding RIL population. Their association with leaf [Na+] and salt tolerance in tomato is also discussed. 相似文献
97.
Dariusz Brzezinski Marcin Kowiel David R. Cooper Marcin Cymborowski Marek Grabowski Alexander Wlodawer Zbigniew Dauter Ivan G. Shabalin Miroslaw Gilski Bernhard Rupp Mariusz Jaskolski Wladek Minor 《Protein science : a publication of the Protein Society》2021,30(1):115-124
The COVID‐19 pandemic has triggered numerous scientific activities aimed at understanding the SARS‐CoV‐2 virus and ultimately developing treatments. Structural biologists have already determined hundreds of experimental X‐ray, cryo‐EM, and NMR structures of proteins and nucleic acids related to this coronavirus, and this number is still growing. To help biomedical researchers, who may not necessarily be experts in structural biology, navigate through the flood of structural models, we have created an online resource, covid19.bioreproducibility.org, that aggregates expert‐verified information about SARS‐CoV‐2‐related macromolecular models. In this article, we describe this web resource along with the suite of tools and methodologies used for assessing the structures presented therein. 相似文献
98.
Chicken liver Cd, Zn-thionein (metallothionein) was isolated from Cd-pretreated chickens weighing 1 500 g. The native Cd, Zn-thionein contained 9 g-atoms of metals per 12 000 g of protein. Upon the addition of Cu(CH3CN)4ClO4, all Cd2 and Zn2 were successfully replaced. 15 g-atoms of Cu from the acetonitrile perchlorate complex were bound to the protein. Due to the absence of aromatic amino acid residues, thionein has unique ultraviolet and circular dichroism properties. The shoulder of the ultraviolet spectrum at 250 nm (A250 X A280(-1) = 23.9) was shifted to 275 nm (A250 X A280(-1) = 1.6). No significant absorption was detected in the visible region. Th conformational changes of the protein moiety were much more visible in the circular dichroism spectra. The titration with Cu(CH3CH)2 caused the appearence of three new Cotton effects: 257.5 nm (+), 350 nm (+) and 301 nm (-). The negative Cotton effect at 239 nm of the original metallothionein was completely levelled off. The binding strength of copper with thionein is extraordinarily high: it survives proton treatment up to pH 1.9. Displacement of the Cd2 by Cu employing Cd-thionein which was formed at pH 2.2 resulted in the same circular dichroism properties as observed for Cu-thionein. D-Penicillamine proved a suitable model for the metal-free thionein, since redox reactions and polymerization of the sterically hindered thiol residue are known to be slow. The correlation of the circular dichroism properties of either copper complex using thionein or D-penicillamine was surprisingly high. Circular dichroism measurements of Cu(I)-D-penicillamine revealed Cotton effects at 255 nm (+), 280 nm (+) and 355 nm (-). Upon examining the red-violet mixed Cu(-i)-cu(II)-D-penicillamine complex, Cotton bands in the visible region at 425 nm (-) and 495 nm (+) were seen. In many blue copper enzymes, the copper is assumed to be in the neighborhood of both cysteine and aromatic amino acid residues, which are known to play an important role in the electron transfer. This is not the case in the Cu-thionein, which would explain many different properties of this copper protein. It is very attractive to conclude that the sterically hindered SH-group of D-penicillamine reacts with excess copper in a specific way, similar to the Cu-thionein. This phenomenon could explain the considerable success of D-penicillamine in the treatment of Wilson's disease. 相似文献
99.
SorCS1 variants and amyloid precursor protein (APP) are co‐transported in neurons but only SorCS1c modulates anterograde APP transport 下载免费PDF全文
Guido Hermey Nadine Schmidt Björn Bluhm Daniel Mensching Kristina Ostermann Carsten Rupp Dietmar Kuhl Stefan Kins 《Journal of neurochemistry》2015,135(1):60-75
Processing of amyloid precursor protein (APP) into amyloid‐β peptide (Aβ) is crucial for the development of Alzheimer's disease (AD). Because this processing is highly dependent on its intracellular itinerary, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated. The sorting receptor SorCS1 has been genetically linked to AD, but the underlying molecular mechanisms are poorly understood. We analyze two SorCS1 variants; one, SorCS1c, conveys internalization of surface‐bound ligands whereas the other, SorCS1b, does not. In agreement with previous studies, we demonstrate co‐immunoprecipitation and co‐localization of both SorCS1 variants with APP. Our results suggest that SorCS1c and APP are internalized independently, although they mostly share a common post‐endocytic pathway. We introduce functional Venus‐tagged constructs to study SorCS1b and SorCS1c in living cells. Both variants are transported by fast anterograde axonal transport machinery and about 30% of anterograde APP‐positive transport vesicles contain SorCS1. Co‐expression of SorCS1b caused no change of APP transport kinetics, but SorCS1c reduced the anterograde transport rate of APP and increased the number of APP‐positive stationary vesicles. These data suggest that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles.
100.