全文获取类型
收费全文 | 1991篇 |
免费 | 250篇 |
出版年
2023年 | 15篇 |
2022年 | 27篇 |
2021年 | 74篇 |
2020年 | 26篇 |
2019年 | 36篇 |
2018年 | 40篇 |
2017年 | 40篇 |
2016年 | 67篇 |
2015年 | 121篇 |
2014年 | 113篇 |
2013年 | 127篇 |
2012年 | 173篇 |
2011年 | 137篇 |
2010年 | 65篇 |
2009年 | 64篇 |
2008年 | 57篇 |
2007年 | 87篇 |
2006年 | 80篇 |
2005年 | 67篇 |
2004年 | 47篇 |
2003年 | 50篇 |
2002年 | 51篇 |
2001年 | 28篇 |
2000年 | 27篇 |
1999年 | 30篇 |
1998年 | 18篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 19篇 |
1992年 | 21篇 |
1991年 | 17篇 |
1990年 | 23篇 |
1989年 | 24篇 |
1988年 | 30篇 |
1987年 | 32篇 |
1986年 | 28篇 |
1985年 | 29篇 |
1984年 | 24篇 |
1983年 | 24篇 |
1982年 | 19篇 |
1981年 | 24篇 |
1980年 | 11篇 |
1979年 | 17篇 |
1978年 | 16篇 |
1976年 | 11篇 |
1974年 | 12篇 |
1973年 | 19篇 |
1972年 | 12篇 |
1971年 | 15篇 |
1970年 | 11篇 |
排序方式: 共有2241条查询结果,搜索用时 46 毫秒
991.
Michael Forster Peter Forster Abdou Elsharawy Georg Hemmrich Benjamin Kreck Michael Wittig Ingo Thomsen Bj?rn Stade Matthias Barann David Ellinghaus Britt-Sabina Petersen Sandra May Espen Melum Markus B. Schilhabel Andreas Keller Stefan Schreiber Philip Rosenstiel Andre Franke 《Nucleic acids research》2013,41(1):e16
Scientists working with single-nucleotide variants (SNVs), inferred by next-generation sequencing software, often need further information regarding true variants, artifacts and sequence coverage gaps. In clinical diagnostics, e.g. SNVs must usually be validated by visual inspection or several independent SNV-callers. We here demonstrate that 0.5–60% of relevant SNVs might not be detected due to coverage gaps, or might be misidentified. Even low error rates can overwhelm the true biological signal, especially in clinical diagnostics, in research comparing healthy with affected cells, in archaeogenetic dating or in forensics. For these reasons, we have developed a package called pibase, which is applicable to diploid and haploid genome, exome or targeted enrichment data. pibase extracts details on nucleotides from alignment files at user-specified coordinates and identifies reproducible genotypes, if present. In test cases pibase identifies genotypes at 99.98% specificity, 10-fold better than other tools. pibase also provides pair-wise comparisons between healthy and affected cells using nucleotide signals (10-fold more accurately than a genotype-based approach, as we show in our case study of monozygotic twins). This comparison tool also solves the problem of detecting allelic imbalance within heterozygous SNVs in copy number variation loci, or in heterogeneous tumor sequences. 相似文献
992.
Sabine Siegert Jochen Hampe Clemens Schafmayer Witigo von Schönfels Jan-Hendrik Egberts Asta Försti Bowang Chen Jesús Lascorz Kari Hemminki Andre Franke Michael Nothnagel Ute Nöthlings Michael Krawczak 《Human genetics》2013,132(2):219-231
Colorectal cancer (CRC), one of the most frequent neoplasias worldwide, has both genetic and environmental causes. As yet, however, gene–environment (G × E) interactions in CRC have been studied mostly for a small number of candidate genes only. Therefore, we investigated the possible interaction, in CRC etiology, between single-nucleotide polymorphisms (SNPs) on the one hand, and overweight, smoking and alcohol consumption on the other, at a genome-wide level. To this end, we adopted a two-tiered approach comprising a case-only screening stage I (314 cases) and a case–control validation stage II (259 cases, 1,002 controls). Interactions with the smallest p value in stage I were verified in stage II using multiple logistic regression analysis adjusted for sex and age. In addition, we specifically studied known CRC-associated SNPs for possible G × E interactions. Upon adjustment for sex and age, and after allowing for multiple testing, however, only a single SNP (rs1944511) was found to be involved in a statistically significant interaction, namely with overweight (multiplicity-corrected p = 0.042 in stage II). Several other G × E interactions were nominally significant but failed correction for multiple testing, including a previously reported interaction between rs9929218 and alcohol consumption that also emerged in our candidate SNP study (nominal p = 0.008). Notably, none of the interactions identified in our genome-wide analysis was with a previously reported CRC-associated SNP. Our study therefore highlights the potential of an “agnostic” genome-wide approach to G × E analysis. 相似文献
993.
994.
Jean-Fran?ois Ginglinger Benoit Boachon René H?fer Christian Paetz Tobias G. K?llner Laurence Miesch Raphael Lugan Raymonde Baltenweck Jér?me Mutterer Pascaline Ullmann Franziska Beran Patricia Claudel Francel Verstappen Marc J.C. Fischer Francis Karst Harro Bouwmeester Michel Miesch Bernd Schneider Jonathan Gershenzon Jürgen Ehlting Danièle Werck-Reichhart 《The Plant cell》2013,25(11):4640-4657
The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus predicted to be involved in monoterpenoid metabolism. We show that all four selected genes, the two terpene synthases (TPS10 and TPS14) and the two cytochrome P450s (CYP71B31 and CYP76C3), are simultaneously expressed at anthesis, mainly in upper anther filaments and in petals. Upon transient expression in Nicotiana benthamiana, the TPS enzymes colocalize in vesicular structures associated with the plastid surface, whereas the P450 proteins were detected in the endoplasmic reticulum. Whether they were expressed in Saccharomyces cerevisiae or in N. benthamiana, the TPS enzymes formed two different enantiomers of linalool: (−)-(R)-linalool for TPS10 and (+)-(S)-linalool for TPS14. Both P450 enzymes metabolize the two linalool enantiomers to form different but overlapping sets of hydroxylated or epoxidized products. These oxygenated products are not emitted into the floral headspace, but accumulate in floral tissues as further converted or conjugated metabolites. This work reveals complex linalool metabolism in Arabidopsis flowers, the ecological role of which remains to be determined. 相似文献
995.
Franziska Anni Franke Fabian Schmidt Christin Borgwardt Detlef Bernhard Christoph Bleidorn Wolf-Eberhard Engelmann Martin Schlegel 《Organisms Diversity & Evolution》2013,13(2):255-266
The endangered African dwarf crocodile Osteolaemus tetraspis is distributed in Central and Western Africa. Conventionally, two subspecies were distinguished: Osteolaemus tetraspis tetraspis and Osteolaemus tetraspis osborni. The taxonomic significance of diagnostic morphological characters is still being discussed and the existence of additional species in the Osteolaemus group remains unclear. Recent molecular studies suggest the existence of three allopatric species in the genus Osteolaemus. These results supported a division of the dwarf crocodile into a Congo Basin form (O. osborni), an Ogooué Basin form (O. tetraspis), and a third separate evolutionary lineage from Western Africa. Several European zoos host African dwarf crocodiles. For reasons of conservation and possible reintroduction, it is important to clarify provenance of these zoo animals. Therefore, we conducted molecular and phylogenetic analyses of three mitochondrial and two nuclear gene sequences with all available samples from European zoos and museums. We also estimated the origin of the zoo animals by comparing sequences of wild animals and museum samples of known provenance. Our study strongly supports three distinct lineages of Osteolaemus as recently postulated, but also reveals a fourth evolutionary lineage. We demonstrate that, of the European zoo animals sampled, only one dwarf crocodile corresponds to the Congo Basin form (O. osborni) whereas the majority of individuals correspond to the three other forms. Four zoo animals belong to the new fourth group; but their provenance is still unresolved. The origin of these animals is probably located in an African region from which no wild animal samples are currently available. Further investigations and sampling of other regions should be completed to clarify the identity of this fourth lineage. We found potential hybrids from European zoological gardens using nuclear DNA sequences. The European Studbook will use these results for further breeding programmes to keep genetically suitable ex-situ populations as reassurance colonies for prospective reintroduction into African countries. 相似文献
996.
Franziska Thomas 《Journal of peptide science》2013,19(3):141-147
The chemical synthesis of proteins has facilitated functional studies of proteins due to the site‐specific incorporation of post‐translational modifications, labels, and non‐proteinogenic amino acids. Moreover, native chemical ligation provides facile access to proteins by chemical means. However, the application of the native chemical ligation reaction in the synthesis of parallel formats such as protein arrays has been complicated because of the often cumbersome and time‐consuming synthesis of the required peptide thioesters. An Fmoc‐based peptide thioester synthesis with self‐purification on the sulfonamide ‘safety‐catch’ linker widens this bottleneck because HPLC purification can be avoided. The method is based on an on‐resin cyclization–thiolysis reaction sequence. A macrocyclization via the N‐terminus of the full‐length peptide followed by a thiolytic C‐terminal ring opening allows selective detachment of the truncation products and the full‐length peptide. A brief overview of the chemical aspects of this method is provided including the optimization steps and the automation process. Furthermore, the application of the cyclization–thiolysis approach combined with the native chemical ligation reaction in the parallel synthesis of a library of 16 SH3‐domain variants of SHO1 in yeast is described, demonstrating the value of this new technique for the chemical synthesis of protein arrays. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
997.
998.
Cichon S Mühleisen TW Degenhardt FA Mattheisen M Miró X Strohmaier J Steffens M Meesters C Herms S Weingarten M Priebe L Haenisch B Alexander M Vollmer J Breuer R Schmäl C Tessmann P Moebus S Wichmann HE Schreiber S Müller-Myhsok B Lucae S Jamain S Leboyer M Bellivier F Etain B Henry C Kahn JP Heath S;Bipolar Disorder Genome Study 《American journal of human genetics》2011,(3):556-381
We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10−8; odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10−4; odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 × 10−9 (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies. 相似文献
999.
John Couwenberg Annett Thiele Franziska Tanneberger J��rgen Augustin Susanne B?risch Dimitry Dubovik Nadzeya Liashchynskaya Dierk Michaelis Merten Minke Arkadi Skuratovich Hans Joosten 《Hydrobiologia》2011,674(1):67-89
Drained peatlands in temperate Europe are a globally important source of greenhouse gas (GHG) emissions. This article outlines a methodology to assess emissions and emission reductions from peatland rewetting projects using vegetation as a proxy. Vegetation seems well qualified for indicating GHG fluxes from peat soils as it reflects long-term water level, affects GHG emissions via assimilate supply and aerenchyma and allows fine-scaled mapping. The methodology includes mapping of vegetation types characterised by the presence and absence of species groups indicative for specific water level classes. GHG flux values are assigned to the vegetation types following a standardized protocol and using published emission values from plots with similar vegetation and water level in regions with similar climate and flora. Carbon sequestration in trees is accounted for by estimating the annual sequestration in tree biomass from forest inventory data. The method follows the criteria of the Voluntary Carbon Standard and is illustrated using the example of two Belarusian peatlands. 相似文献
1000.
Cancer results from the accumulation of alterations in oncogenes and tumor suppressor genes. Tumor suppressors are classically defined as genes which contribute to tumorigenesis if their function is lost. Genetic or epigenetic alterations inactivating such genes may arise during somatic cell divisions or alternatively may be inherited from a parent. One notable exception to this rule is the BRCA1 tumor suppressor that predisposes to hereditary breast cancer when lost. Genetic alterations of this gene are hardly ever observed in sporadic breast cancer, while individuals harboring a germline mutation readily accumulate a second alteration inactivating the remaining allele—a finding which represents a conundrum in cancer genetics. In this paper, we present a novel mathematical framework of sporadic and hereditary breast tumorigenesis. We study the dynamics of genetic alterations driving breast tumorigenesis and explore those scenarios which can explain the absence of somatic BRCA1 alterations while replicating all other disease statistics. Our results support the existence of a heterozygous phenotype of BRCA1 and suggest that the loss of one BRCA1 allele may suppress the fitness advantage caused by the inactivation of other tumor suppressor genes. This paper contributes to the mathematical investigation of breast tumorigenesis. 相似文献