全文获取类型
收费全文 | 39993篇 |
免费 | 4139篇 |
国内免费 | 11篇 |
专业分类
44143篇 |
出版年
2023年 | 175篇 |
2022年 | 349篇 |
2021年 | 670篇 |
2020年 | 486篇 |
2019年 | 566篇 |
2018年 | 702篇 |
2017年 | 631篇 |
2016年 | 1044篇 |
2015年 | 1727篇 |
2014年 | 1882篇 |
2013年 | 2329篇 |
2012年 | 2866篇 |
2011年 | 2784篇 |
2010年 | 1849篇 |
2009年 | 1611篇 |
2008年 | 2247篇 |
2007年 | 2235篇 |
2006年 | 2126篇 |
2005年 | 1895篇 |
2004年 | 1888篇 |
2003年 | 1681篇 |
2002年 | 1653篇 |
2001年 | 653篇 |
2000年 | 612篇 |
1999年 | 622篇 |
1998年 | 434篇 |
1997年 | 352篇 |
1996年 | 339篇 |
1995年 | 350篇 |
1994年 | 309篇 |
1993年 | 305篇 |
1992年 | 414篇 |
1991年 | 354篇 |
1990年 | 349篇 |
1989年 | 365篇 |
1988年 | 366篇 |
1987年 | 337篇 |
1986年 | 268篇 |
1985年 | 299篇 |
1984年 | 303篇 |
1983年 | 269篇 |
1982年 | 257篇 |
1981年 | 231篇 |
1980年 | 209篇 |
1979年 | 216篇 |
1978年 | 182篇 |
1977年 | 183篇 |
1976年 | 182篇 |
1975年 | 198篇 |
1973年 | 164篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Matt Turner Seth Eidemiller Bryan Martin Andrew Narver Joshua Marshall Logan Zemp Kenneth A. Cornell J.M. McIntosh Owen M. McDougal 《Bioorganic & medicinal chemistry》2009,17(16):5894-5899
Parkinson’s disease is a debilitating movement disorder characterized by altered levels of α6β21 (1 indicates the possible presence of additional subunits) nicotinic acetylcholine receptors (nAChRs) localized on presynaptic striatal catecholaminergic neurons. α-Conotoxin MII (α-CTx MII) is a highly useful ligand to probe α6β2 nAChRs structure and function, but it does not discriminate among closely related α61 nAChR subtypes. Modification of the α-CTx MII primary sequence led to the identification of α-CTx MII[E11A], an analog with 500–5300-fold discrimination between α61 subtypes found in both human and non-human primates. α-CTx MII[E11A] binds most strongly (femtomolar dissociation constant) to the high affinity α6 nAChR, a subtype that is selectively lost in Parkinson’s disease. Here, we present the three-dimensional solution structure for α-CTx MII[E11A] as determined by two-dimensional 1H NMR spectroscopy to 0.13 ± 0.09 ? backbone and 0.45 ± 0.08 ? heavy atom root-mean-square deviation from mean structure. Structural comparisons suggest that the increased hydrophobic area of α-CTx MII[E11A] relative to other members of the α-CTx family may be responsible for its exceptionally high affinity for α6α4β21 nAChR as well as discrimination between α6β2 and α3β2 containing nAChRs. This finding may enable the rational design of novel peptide analogs that demonstrate enhanced specificity for α61 nAChR subunit interfaces and provide a means to better understand nAChR structural determinants that modulate brain dopamine levels and the pathophysiology of Parkinson’s disease. 相似文献
992.
The interactions among plants and pollinators are crucial for plant reproduction because they structure gene flow among individual plants and among populations of plants. Throughout the Neotropics there has been a strong increase in recent years in the use of artificial nectar feeders in private nature reserves to encourage ecotourism through prolonged observations of hummingbirds. Currently, there is considerable uncertainty whether artificial feeders have a detrimental effect on plant reproduction through competition or a beneficial effect through facilitation. This uncertainty is disconcerting given that nature reserves harbour many rare and endangered plants whose successful reproduction is a conservation goal. To assess whether nectar feeders affected hummingbird visitation to flowering plants, we determined visitation rates in ten flowering species in five Andean nature reserves in Ecuador. We found that visitation rates tended to be higher within 5 m around the feeders than they were at 100 m, 500 m, or 1.5 km distance to the feeders, therefore indicating that nectar feeders tended to facilitate flower visitation at close distance. Because visitation rates at 100 m and 500 m distance from the feeders did not differ from those at 1.5 km, we suggest that feeders do not draw hummingbirds away from flower resources, but if they have an effect on flower visitation at all, they tend to facilitate flower visitation rather than reduce plant reproduction. 相似文献
993.
994.
For many targets of pharmaceutical importance conformational changes of the receptor protein are relevant during the ligand binding process. A new docking approach, ReFlexIn (Receptor Flexibility by Interpolation), that combines receptor flexibility with the computationally efficient potential grid representation of receptor molecules has been evaluated on the retroviral HIV-1 (Human Immunodeficiency Virus 1) protease system. An approximate inclusion of receptor flexibility is achieved by using interpolation between grid representations of individual receptor conformations. For the retroviral protease the method was tested on an ensemble of protease structures crystallized in the presence of different ligands and on a set of structures obtained from morphing between the unbound and a ligand-bound protease structure. Docking was performed on ligands known to bind to the protease and several non-binders. For the binders the ReFlexIn method yielded in almost all cases ligand placements in similar or closer agreement with experiment than docking to any of the ensemble members without degrading the discrimination with respect to non-binders. The improved docking performance compared to docking to rigid receptors allows for systematic virtual screening applications at very small additional computational cost. 相似文献
995.
996.
Lauren F. Messer Martin Ostrowski Martina A. Doblin Katherina Petrou Mark E. Baird Timothy Ingleton Andrew Bissett Jodie Van de Kamp Tiffanie Nelson Ian Paulsen Levente Bodrossy Jed A. Fuhrman Justin R. Seymour Mark V. Brown 《Global Change Biology》2020,26(10):5613-5629
Western boundary currents (WBCs) redistribute heat and oligotrophic seawater from the tropics to temperate latitudes, with several displaying substantial climate change‐driven intensification over the last century. Strengthening WBCs have been implicated in the poleward range expansion of marine macroflora and fauna, however, the impacts on the structure and function of temperate microbial communities are largely unknown. Here we show that the major subtropical WBC of the South Pacific Ocean, the East Australian Current (EAC), transports microbial assemblages that maintain tropical and oligotrophic (k‐strategist) signatures, to seasonally displace more copiotrophic (r‐strategist) temperate microbial populations within temperate latitudes of the Tasman Sea. We identified specific characteristics of EAC microbial assemblages compared with non‐EAC assemblages, including strain transitions within the SAR11 clade, enrichment of Prochlorococcus, predicted smaller genome sizes and shifts in the importance of several functional genes, including those associated with cyanobacterial photosynthesis, secondary metabolism and fatty acid and lipid transport. At a temperate time‐series site in the Tasman Sea, we observed significant reductions in standing stocks of total carbon and chlorophyll a, and a shift towards smaller phytoplankton and carnivorous copepods, associated with the seasonal impact of the EAC microbial assemblage. In light of the substantial shifts in microbial assemblage structure and function associated with the EAC, we conclude that climate‐driven expansions of WBCs will expand the range of tropical oligotrophic microbes, and potentially profoundly impact the trophic status of temperate waters. 相似文献
997.
Walter Rossi Cervi Rubens Augusto Camargo Lamparelli Joaquim Eugênio Abel Seabra Martin Junginger Sierk de Jong Floor van der Hilst 《Global Change Biology Bioenergy》2020,12(2):136-157
It is expected that Brazil could play an important role in biojet fuel (BJF) production in the future due to the long experience in biofuel production and the good agro‐ecological conditions. However, it is difficult to quantify the techno‐economic potential of BJF because of the high spatiotemporal variability of available land, biomass yield, and infrastructure as well as the technological developments in BJF production pathways. The objective of this research is to assess the recent and future techno‐economic potential of BJF production in Brazil and to identify location‐specific optimal combinations of biomass crops and technological conversion pathways. In total, 13 production routes (supply chains) are assessed through the combination of various biomass crops and BJF technologies. We consider temporal land use data to identify potential land availability for biomass production. With the spatial distribution of the land availability and potential yield of biomass crops, biomass production potential and costs are calculated. The BJF production cost is calculated by taking into account the development in the technological pathways and in plant scales. We estimate the techno‐economic potential by determining the minimum BJF total costs and comparing this with the range of fossil jet fuel prices. The techno‐economic potential of BJF production ranges from 0 to 6.4 EJ in 2015 and between 1.2 and 7.8 EJ in 2030, depending on the reference fossil jet fuel price, which varies from 19 to 65 US$/GJ across the airports. The techno‐economic potential consists of a diverse set of production routes. The Northeast and Southeast region of Brazil present the highest potentials with several viable production routes, whereas the remaining regions only have a few promising production routes. The maximum techno‐economic potential of BJF in Brazil could meet almost half of the projected global jet fuel demand toward 2030. 相似文献
998.
Neele Wendler Martin Mascher Christiane Nöh Axel Himmelbach Uwe Scholz Brigitte Ruge‐Wehling Nils Stein 《Plant biotechnology journal》2014,12(8):1122-1131
Crop wild relatives (CWR) provide an important source of allelic diversity for any given crop plant species for counteracting the erosion of genetic diversity caused by domestication and elite breeding bottlenecks. Hordeum bulbosum L. is representing the secondary gene pool of the genus Hordeum. It has been used as a source of genetic introgressions for improving elite barley germplasm (Hordeum vulgare L.). However, genetic introgressions from H. bulbosum have yet not been broadly applied, due to a lack of suitable molecular tools for locating, characterizing, and decreasing by recombination and marker‐assisted backcrossing the size of introgressed segments. We applied next‐generation sequencing (NGS) based strategies for unlocking genetic diversity of three diploid introgression lines of cultivated barley containing chromosomal segments of its close relative H. bulbosum. Firstly, exome capture‐based (re)‐sequencing revealed large numbers of single nucleotide polymorphisms (SNPs) enabling the precise allocation of H. bulbosum introgressions. This SNP resource was further exploited by designing a custom multiplex SNP genotyping assay. Secondly, two‐enzyme‐based genotyping‐by‐sequencing (GBS) was employed to allocate the introgressed H. bulbosum segments and to genotype a mapping population. Both methods provided fast and reliable detection and mapping of the introgressed segments and enabled the identification of recombinant plants. Thus, the utilization of H. bulbosum as a resource of natural genetic diversity in barley crop improvement will be greatly facilitated by these tools in the future. 相似文献
999.
Daniel F. Gudbjartsson Hilma Holm Olafur S. Indridason Gudmar Thorleifsson Vidar Edvardsson Patrick Sulem Femmie de Vegt Frank C. H. d'Ancona Martin den Heijer Leifur Franzson Thorunn Rafnar Kristleifur Kristjansson Unnur S. Bjornsdottir Gudmundur I. Eyjolfsson Lambertus A. Kiemeney Augustine Kong Runolfur Palsson Unnur Thorsteinsdottir Kari Stefansson 《PLoS genetics》2010,6(7)
Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1×10−10). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3×10−23) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0×10−17) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0×10−6), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7×10−5). 相似文献
1000.
Thangstad OP Gilde B Chadchawan S Seem M Husebye H Bradley D Bones AM 《Plant molecular biology》2004,54(4):597-611
A prototypical characteristic of the Brassicaceae is the presence of the myrosinase-glucosinolate system. Myrosinase, the only known S-glycosidase in plants, degrades glucosinolates, thereby initiating the formation of isothiocyanates, nitriles and other reactive products with biological activities. We have used myrosinase gene promoters from Brassica napus and Arabidopsis thaliana fused to the beta -glucuronidase (GUS) reporter gene and introduced into Arabidopsis thaliana, Brassica napus and/or Nicotiana tabacum plants to compare and determine the cell types expressing the myrosinase genes and the GUS expression regulated by these promoters. The A. thaliana TGG1 promoter directs expression to guard cells and phloem myrosin cell idioblasts of transgenic A. thaliana plants. Expression from the same promoter construct in transgenic tobacco plants lacking the myrosinase enzyme system also directs expression to guard cells. The B. napus Myr1.Bn1 promoter directs a cell specific expression to idioblast myrosin cells of immature and mature seeds and myrosin cells of phloem of B. napus. In A. thaliana the B. napus promoter directs expression to guard cells similar to the expression pattern of TGG1. The Myr1.Bn1 signal peptide targets the gene product to the reticular myrosin grains of myrosin cells. Our results indicate that myrosinase gene promoters from Brassicaceae direct cell, organ and developmental specific expression in B. napus, A. thaliana and N. tabacum. 相似文献