全文获取类型
收费全文 | 1053篇 |
免费 | 75篇 |
出版年
2022年 | 7篇 |
2021年 | 18篇 |
2020年 | 6篇 |
2019年 | 18篇 |
2018年 | 18篇 |
2017年 | 10篇 |
2016年 | 16篇 |
2015年 | 33篇 |
2014年 | 40篇 |
2013年 | 59篇 |
2012年 | 60篇 |
2011年 | 70篇 |
2010年 | 46篇 |
2009年 | 41篇 |
2008年 | 63篇 |
2007年 | 39篇 |
2006年 | 35篇 |
2005年 | 40篇 |
2004年 | 41篇 |
2003年 | 51篇 |
2002年 | 44篇 |
2001年 | 8篇 |
2000年 | 13篇 |
1999年 | 12篇 |
1998年 | 13篇 |
1996年 | 14篇 |
1994年 | 8篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1987年 | 6篇 |
1985年 | 6篇 |
1982年 | 7篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1973年 | 12篇 |
1966年 | 5篇 |
1957年 | 5篇 |
1956年 | 6篇 |
1953年 | 6篇 |
1939年 | 6篇 |
1935年 | 5篇 |
1932年 | 5篇 |
1930年 | 8篇 |
1929年 | 8篇 |
1927年 | 6篇 |
1915年 | 5篇 |
1905年 | 5篇 |
1896年 | 11篇 |
1894年 | 6篇 |
1887年 | 5篇 |
排序方式: 共有1128条查询结果,搜索用时 390 毫秒
61.
62.
Background
The emergence of structural genomics presents significant challenges in the annotation of biologically uncharacterized proteins. Unfortunately, our ability to analyze these proteins is restricted by the limited catalog of known molecular functions and their associated 3D motifs. 相似文献63.
We have recently obtained evidence favoring the occurrence of an up-regulation of a non-neuronal cholinergic system in chronic painful patellar tendon tendinosis. It seems possible that this up-regulation to a certain degree may be involved in the manifestations of the disease. Today, there is a new, very successful, line of treatment of patellar tendinosis in the form of Doppler guided sclerosing injections. However, a few patients seem resistant to this therapy. Therefore, we have in this pilot study investigated biopsies from the patellar tendon of three such therapy-resistant patients, using immunohistochemistry. In situ hybridization was also applied. Comparisons were made with a material of specimens from both normal (n=16) and tendinosis (n=7) tendons, also previously examined. The study showed that there were extensive immunoreactions for choline acetyltransferase (ChAT) and vesicular acetylcholine transporter, as well as for the M(2) muscarinic acetylcholine receptor, in the overwhelming majority of the tenocytes. The immunoreactions were more pronounced than those generally obtained in the tendinosis tissue of the previously studied patients and clearly more pronounced than those of patellar tendon tissue of controls. Also, for the first time, we here present findings of mRNA for ChAT within tenocytes. In conclusion, it appears as if there is an excessive local acetylcholine (ACh) production and an occurrence of marked ACh effects in cases of severe tendinosis. An excessive production of local ACh might be related to pain sensation and the processes that occur in tendinosis development, such as cell proliferation. Thus, the results of this pilot study suggest that non-neuronal ACh is highly involved in the pathology of therapy-resistant patellar tendinosis. 相似文献
64.
Quantifying nitrogen (N) fertiliser use efficiency (NFUE) in pastoral systems has important implications for fertiliser management
from both economic and environmental points of view. The potential of a decision tree approach for modelling NFUE in New Zealand
pastures was investigated. The decision tree model suggested that the time of applying N fertiliser was the most important
factor influencing NFUE, with August or September (early spring in New Zealand) being the best time of application. The interaction
of rainfall and temperature, rainfall, phosphorus (P) fertiliser history, soil Olsen P and slope were other important factors
influencing NFUE. The model was validated for 11 of the 16 trials tested with a predictive accuracy of 69%. The mechanisms
by which these factors influenced NFUE and the uncertainty associated with the model prediction were discussed. It was concluded
that this type of modelling approach can be used to predict NFUE and thereby to assist decisions on when and where to apply
N fertiliser in pastures for increasing productivity while reducing the environmental impact. 相似文献
65.
High plasma apolipoprotein B (apoB) and LDL cholesterol levels increase cardiovascular disease risk. These highly correlated measures may be partially controlled by common genetic polymorphisms. To identify chromosomal regions that contain genes causing low plasma levels of one or both parameters in Caucasian families ascertained for familial hypobetalipoproteinemia (FHBL), we conducted a whole-genome scan using 443 microsatellite markers typed in nine multigenerational families with at least two members with FHBL. Both variance components and regression-based linkage methods were used to identify regions of interest. Common linkage regions were identified for both measures on chromosomes 10q25.1-10q26.11 [maximum log of the odds (LOD) = 4.2 for LDL and 3.5 for apoB] and 6q24.3 (maximum LOD = 1.46 for LDL and 1.84 for apoB). There was also evidence for linkage to apoB on chromosome 13q13.2 (LOD = 1.97) and to LDL on chromosome 3p14.1 at 94 centimorgan (LOD = 1.52). Bivariate linkage analysis provided further evidence for loci contributing to both traits (6q24.3, LOD = 1.43; 10q25.1, LOD = 1.74). We evaluated single nucleotide polymorphisms (SNPs) in genes within our linkage regions to identify variants associated with apoB or LDL levels. The most significant finding was for rs2277205 in the 5' untranslated region of acyl-coenzyme A dehydrogenase short/branched chain and LDL (P = 10(-7)). Three additional SNPs were associated with apoB and/or LDL (P < 0.01). Although only the linkage signal on chromosome 10 reached genome-wide statistical significance, there are likely multiple chromosomal regions with variants that contribute to low levels of apoB and LDL and that may protect against coronary heart disease. 相似文献
66.
Heterogeneous ribonucleoprotein m is a splicing regulatory protein that can enhance or silence splicing of alternatively spliced exons 总被引:2,自引:0,他引:2
Splicing of fibroblast growth factor receptor 2 (FGFR2) alternative exons IIIb and IIIc is regulated by the auxiliary RNA cis-element ISE/ISS-3 that promotes splicing of exon IIIb and silencing of exon IIIc. Using RNA affinity chromatography, we have identified heterogeneous nuclear ribonucleoprotein M (hnRNP M) as a splicing regulatory factor that binds to ISE/ISS-3 in a sequence-specific manner. Overexpression of hnRNP M promoted exon IIIc skipping in a cell line that normally includes it, and association of hnRNP M with ISE/ISS-3 was shown to contribute to this splicing regulatory function. Thus hnRNP M, along with other members of the hnRNP family of RNA-binding proteins, plays a combinatorial role in regulation of FGFR2 alternative splicing. We also determined that hnRNP M can affect the splicing of several other alternatively spliced exons. This activity of hnRNP M included the ability not only to induce exon skipping but also to promote exon inclusion. This is the first report demonstrating a role for this abundant hnRNP family member in alternative splicing in mammals and suggests that this protein may broadly contribute to the fidelity of splice site recognition and alternative splicing regulation. 相似文献
67.
Insulin stimulation of the trafficking of the glucose transporter GLUT4 to the plasma membrane is controlled in part by the phosphorylation of the Rab GAP (GTPase-activating protein) AS160 (also known as Tbc1d4). Considerable evidence indicates that the phosphorylation of this protein by Akt (protein kinase B) leads to suppression of its GAP activity and results in the elevation of the GTP form of a critical Rab. The present study examines a similar Rab GAP, Tbc1d1, about which very little is known. We found that the Rab specificity of the Tbc1d1 GAP domain is identical with that of AS160. Ectopic expression of Tbc1d1 in 3T3-L1 adipocytes blocked insulin-stimulated GLUT4 translocation to the plasma membrane, whereas a point mutant with an inactive GAP domain had no effect. Insulin treatment led to the phosphorylation of Tbc1d1 on an Akt site that is conserved between Tbc1d1 and AS160. These results show that Tbc1d1 regulates GLUT4 translocation through its GAP activity, and is a likely Akt substrate. An allele of Tbc1d1 in which Arg(125) is replaced by tryptophan has very recently been implicated in susceptibility to obesity by genetic analysis. We found that this form of Tbc1d1 also inhibited GLUT4 translocation and that this effect also required a functional GAP domain. 相似文献
68.
Molecular density information (as measured by electron microscopic reconstructions or crystallographic density maps) can be a powerful source of information for molecular modeling. Molecular density constrains models by specifying where atoms should and should not be. Low-resolution density information can often be obtained relatively quickly, and there is a need for methods that use it effectively. We have previously described a method for scoring molecular models with surface envelopes to discriminate between plausible and implausible fits. We showed that we could successfully filter out models with the wrong shape based on this discrimination power. Ideally, however, surface information should be used during the modeling process to constrain the conformations that are sampled. In this paper, we describe an extension of our method for using shape information during computational modeling. We use the envelope scoring metric as part of an objective function in a global optimization that also optimizes distances and angles while avoiding collisions. We systematically tested surface representations of proteins (using all nonhydrogen heavy atoms) with different abundance of distance information and showed that the root mean square deviation (RMSD) of models built with envelope information is consistently improved, particularly in data sets with relatively small sets of short-range distances. 相似文献
69.
Natural hypersaline waters are widely distributed around the globe, as both continental surface waters and sea floor lakes, the latter being maintained by the large density difference between the hypersaline and overlying marine water. Owing to the extreme salt concentrations, close to or at saturation (approximately 35%, w/v), such waters might be expected to be devoid of life but, in fact, maintain dense populations of microbes. The majority of these microorganisms are halophilic prokaryotes belonging to the Domain Archaea, 'haloarchaea'. Viruses infecting haloarchaea are a vital part of hypersaline ecosystems, in many circumstances outnumbering cells by 10-100-fold. However, few of these 'haloviruses' have been isolated and even fewer have been characterised in molecular detail. In this review, we explore the methods used by haloviruses to replicate within their hosts and consider the implications of haloviral-haloarchaeal interactions for salt lake ecology. 相似文献
70.
Russ A Kuker Geraldine Mesoloras Seza A Gulec 《International Seminars in Surgical Oncology : ISSO》2007,4(1):17