全文获取类型
收费全文 | 4030篇 |
免费 | 373篇 |
国内免费 | 3篇 |
出版年
2023年 | 27篇 |
2022年 | 58篇 |
2021年 | 131篇 |
2020年 | 79篇 |
2019年 | 92篇 |
2018年 | 115篇 |
2017年 | 106篇 |
2016年 | 170篇 |
2015年 | 309篇 |
2014年 | 275篇 |
2013年 | 270篇 |
2012年 | 444篇 |
2011年 | 359篇 |
2010年 | 230篇 |
2009年 | 186篇 |
2008年 | 267篇 |
2007年 | 240篇 |
2006年 | 196篇 |
2005年 | 189篇 |
2004年 | 132篇 |
2003年 | 129篇 |
2002年 | 107篇 |
2001年 | 17篇 |
2000年 | 18篇 |
1999年 | 12篇 |
1998年 | 27篇 |
1997年 | 9篇 |
1996年 | 8篇 |
1995年 | 12篇 |
1994年 | 10篇 |
1993年 | 12篇 |
1992年 | 16篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1988年 | 12篇 |
1987年 | 5篇 |
1985年 | 5篇 |
1984年 | 13篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1976年 | 4篇 |
1975年 | 8篇 |
1974年 | 4篇 |
1972年 | 4篇 |
1969年 | 4篇 |
1968年 | 4篇 |
排序方式: 共有4406条查询结果,搜索用时 31 毫秒
981.
Polymorphisms at the melanocortin-1 receptor (MC1R) gene have been linked to coloration in many vertebrate species. However, the potentially confounding influence of population structure has rarely been controlled for. We explored the role of the MC1R in a model avian system by sequencing the coding region in 162 zebra finches comprising 79 wild type and 83 white individuals from five stocks. Allelic counts differed significantly between the two plumage morphs at multiple segregating sites, but these were mostly synonymous. To provide a control, the birds were genotyped at eight microsatellites and subjected to Bayesian cluster analysis, revealing two distinct groups. We therefore crossed wild type with white individuals and backcrossed the F1s with white birds. No significant associations were detected in the resulting offspring, suggesting that our original findings were a byproduct of genome-wide divergence. Our results are consistent with a previous study that found no association between MC1R polymorphism and plumage coloration in leaf warblers. They also contribute towards a growing body of evidence suggesting that care should be taken to quantify, and where necessary control for, population structure in association studies. 相似文献
982.
983.
Serene M. L. Lee Celine Schelcher Reinhard Thasler Tobias S. Schiergens Wolfgang E. Thasler 《PloS one》2015,10(9)
The use of banked human tissue, obtained with informed consent after elective surgical procedures, represents a powerful model for understanding underlying mechanisms of diseases or therapeutic interventions and for establishing prognostic markers. However, donated tissues typically have varying times of warm ischaemia in situ due to blood arrest or cold ischaemia due to procurement and transportation. Hence, before using these tissues, it is important to carry out pre-analytical studies to ensure that they are representative of the in vivo state. In particular, tissues of the gastrointestinal tract have been thought to have low RNA stability. Therefore, this study aimed to determine if extended warm or cold ischaemia times and snap-freezing or banking in RNA stabilization solution affects RNA integrity or gene expression in human ileum mucosa. In short, ileum mucosa was collected for up to 1.5 h and 6 h of simulated warm or cold ischaemia respectively. Subsequently, RNA integrity and gene expressions were determined. It was found that RNA integrity remained high over the course of warm and cold ischaemia examined and there were in general no significant differences between snap-freezing and banking in RNA stabilization solution. Following the same trend, there were in general no significant changes in gene expressions measured (MYC, HIF1α, CDX, HMOX1 and IL1β). In conclusion, RNA in the ileum mucosa is maintained at a high integrity and has stable gene expression over the examined time course of warm or cold ischaemia when banked in RNA stabilization solution or snap-frozen in liquid nitrogen. As the average warm and cold ischaemia times imposed by surgery and the process of tissue banking are shorter than the time period examined in this study, human ileum mucosa samples collected after surgeries could be used for gene expression studies. 相似文献
984.
Juan-Carlos T. Gonzalez Ben C. Sheldon Joseph A. Tobias 《Proceedings. Biological sciences / The Royal Society》2013,280(1768)
Reproductive cooperation in social animals has been the focus of intensive research, yet the role of environmental factors in promoting such cooperation remains uncertain. A recent global analysis suggested that cooperative breeding in birds is a ‘bet-hedging’ strategy associated with climatic uncertainty, but it is unclear whether this mechanism applies generally or is restricted to the insectivorous passerines that predominate as cooperative breeders at the global scale. Here, we use a phylogenetic framework to assess the effect of climate on the evolution of cooperation in hornbills (Bucerotidae), an avian family characterized by frugivory and carnivory. We show that, in contrast to the global pattern, cooperative reproduction is positively associated with both inter- and intra-annual climatic stability. This reversed relationship implies that hornbills are relatively insensitive to climatic fluctuations, perhaps because of their dietary niche or increased body mass, both of which may remove the need for bet-hedging. We conclude that the relationship between climatic variability and cooperative breeding is inconsistent across taxa, and potentially mediated by life-history variation. These findings help to explain the mixed results of previous studies and highlight the likely shortcomings of global datasets inherently biased towards particular categories. 相似文献
985.
986.
Tobias Pamminger Susanne Foitzik Katharina C. Kaufmann Natalie Schützler Florian Menzel 《PloS one》2014,9(1)
Division of labor is a defining characteristic of social insects and fundamental to their ecological success. Many of the numerous tasks essential for the survival of the colony must be performed at a specific location. Consequently, spatial organization is an integral aspect of division of labor. The mechanisms organizing the spatial distribution of workers, separating inside and outside workers without central control, is an essential, but so far neglected aspect of division of labor. In this study, we investigate the behavioral mechanisms governing the spatial distribution of individual workers and its physiological underpinning in the ant Myrmica rubra. By investigating worker personalities we uncover position-associated behavioral syndromes. This context-independent and temporally stable set of correlated behaviors (positive association between movements and attraction towards light) could promote the basic separation between inside (brood tenders) and outside workers (foragers). These position-associated behavior syndromes are coupled with a high probability to perform tasks, located at the defined position, and a characteristic cuticular hydrocarbon profile. We discuss the potentially physiological causes for the observed behavioral syndromes and highlight how the study of animal personalities can provide new insights for the study of division of labor and self-organized processes in general. 相似文献
987.
Jessica L. Porter Nicholas J. Tobias Sacha J. Pidot Steffen Falgner Kellie L. Tuck Andrea Vettiger Hui Hong Peter F. Leadlay Timothy P. Stinear 《PloS one》2013,8(7)
Mycolactones are polyketide-derived lipid virulence factors made by the slow-growing human pathogen, Mycobacterium ulcerans. Three unusually large and homologous plasmid-borne genes (mlsA1: 51 kb, mlsB: 42 kb and mlsA2: 7 kb) encode the mycolactone type I polyketide synthases (PKS). The extreme size and low sequence diversity of these genes has posed significant barriers for exploration of the genetic and biochemical basis of mycolactone synthesis. Here, we have developed a truncated, more tractable 3-module version of the 18-module mycolactone PKS and we show that this engineered PKS functions as expected in the natural host M. ulcerans to produce an additional polyketide; a triketide lactone (TKL). Cell fractionation experiments indicated that this 3-module PKS and the putative accessory enzymes encoded by mup045 and mup038 associated with the mycobacterial cell wall, a finding supported by confocal microscopy. We then assessed the capacity of the faster growing, Mycobacterium marinum to harbor and express the 3-module Mls PKS and accessory enzymes encoded by mup045 and mup038. RT-PCR, immunoblotting, and cell fractionation experiments confirmed that the truncated Mls PKS multienzymes were expressed and also partitioned with the cell wall material in M. marinum. However, this heterologous host failed to produce TKL. The systematic deconstruction of the mycolactone PKS presented here suggests that the Mls multienzymes are necessary but not sufficient for mycolactone synthesis and that synthesis is likely to occur (at least in part) within the mycobacterial cell wall. This research is also the first proof-of-principle demonstration of the potential of this enzyme complex to produce tailored small molecules through genetically engineered rearrangements of the Mls modules. 相似文献
988.
H. Scheffer Rein P. Stulp Edwin Verlind M. van der Meulen Leena Bruckner-Tuderman Tobias Gedde-Dahl Jr. G. J. te Meerman Arnoud Sonnenberg Charles H. C. M. Buys Marcel F. Jonkman 《Human genetics》1997,100(2):230-235
Generalised atrophic benign epidermolysis bullosa (GABEB) is a form of junctional epidermolysis bullosa with a recessive
mode of inheritance. The gene considered likely to be involved in this disease is COL17A1, since in the majority of GABEB
patients the product of that gene, the 180-kD bullous pemphigoid antigen (BP180), is undetectable in skin. We have identified
an intragenic COL17A1 microsatellite marker for which 83% of randomly selected control individuals are heterozygous. We observed
homozygosity for different alleles of this marker in five out of six collagen type XVII-negative GABEB patients of different
European descent. Five of the six COL17A1 alleles of three patients originating from the eastern part of The Netherlands were
identical, as were the haplotypes including flanking markers. The 2342delG mutation was identified in all these five alleles.
This confirms the expectation that due to genetic drift and hidden inbreeding for an autosomal recessive disorder with low
gene frequency, such as collagen type XVII-negative GABEB, most disease alleles from a restricted geographical area will be
“identical by descent”. Our results demonstrate that involvement of a candidate gene can be confirmed by looking for identity
by descent of highly informative intragenic markers.
Received: 25 October 1996 / Accepted: 6 March 1997 相似文献
989.
In order to investigate the role of nonpolar side chains in determining protein stability, we have carried out a molecular dynamics simulation study of the thermodynamics of interconverting isoleucine and valine side chains in the core of ribonuclease T1. The free energy change in the unfolded state, which we take to be fully solvated, was small and agrees qualitatively with experimental studies of alkane solvation. In the two Ile----Val mutations studied, the protein was able to relax around the smaller side chains, while in the case of the two Val----Ile mutations, the ability of the core to accommodate the extra methylene group depended on where the mutation took place. We argue that the experimentally observed decrease in stability for mutating isoleucine into valine results from a loss of favorable packing interactions of the side chain in the folded form of the protein. This supports the view that packing interactions in the folded state are an important contributor to the overall stability of the folded protein and that the core of the native protein is packed efficiently and almost completely. 相似文献
990.