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61.
62.
A number of 5′, N6- and C8, N6-disubstituted adenosine analogs was synthesized and tested for inhibition of trypanosomal glyceraldehyde 3-phosphate dehydrogenase. The most active compound, N6-(3-methyl-2-butenyl)-8-(2-thienyl)adenosine, had Ki of 9 μM and was marginally selective for the parasite enzyme. 相似文献
63.
María Pérez-Fernández Carole P. Elliott Alex Valentine José Antonio Oyola 《Journal of Plant Ecology》2019,12(6):949
Aims
Seeds ofRumex crispusfrom six provenances were studied in relation to their germination under drought and presence of nitrogen in the germination and emergence media. We also investigated whether adaptation to soil increases the ability of the species to colonize and establish in contrasting environments along a longitudinal gradient in western Spain by means of a reciprocal transplantation experiment. 相似文献
64.
Genetic and environmental influences on migraine: a twin study across six countries. 总被引:7,自引:0,他引:7
Elles J Mulder Caroline Van Baal David Gaist Mikko Kallela Jaakko Kaprio Dan A Svensson Dale R Nyholt Nicholas G Martin Alex J MacGregor Lynn F Cherkas Dorret I Boomsma Aarno Palotie 《Twin research》2003,6(5):422-431
Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine. 相似文献
65.
Base excision repair is limited by different proteins in male germ cell nuclear extracts prepared from young and old mice 总被引:3,自引:0,他引:3 下载免费PDF全文
Intano GW McMahan CA McCarrey JR Walter RB McKenna AE Matsumoto Y MacInnes MA Chen DJ Walter CA 《Molecular and cellular biology》2002,22(7):2410-2418
The combined observations of elevated DNA repair gene expression, high uracil-DNA glycosylase-initiated base excision repair, and a low spontaneous mutant frequency for a lacI transgene in spermatogenic cells from young mice suggest that base excision repair activity is high in spermatogenic cell types. Notably, the spontaneous mutant frequency of the lacI transgene is greater in spermatogenic cells obtained from old mice, suggesting that germ line DNA repair activity may decline with age. A paternal age effect in spermatogenic cells is recognized for the human population as well. To determine if male germ cell base excision repair activity changes with age, uracil-DNA glycosylase-initiated base excision repair activity was measured in mixed germ cell (i.e., all spermatogenic cell types in adult testis) nuclear extracts prepared from young, middle-aged, and old mice. Base excision repair activity was also assessed in nuclear extracts from premeiotic, meiotic, and postmeiotic spermatogenic cell types obtained from young mice. Mixed germ cell nuclear extracts exhibited an age-related decrease in base excision repair activity that was restored by addition of apurinic/apyrimidinic (AP) endonuclease. Uracil-DNA glycosylase and DNA ligase were determined to be limiting in mixed germ cell nuclear extracts prepared from young animals. Base excision repair activity was only modestly elevated in pachytene spermatocytes and round spermatids relative to other spermatogenic cells. Thus, germ line short-patch base excision repair activity appears to be relatively constant throughout spermatogenesis in young animals, limited by uracil-DNA glycosylase and DNA ligase in young animals, and limited by AP endonuclease in old animals. 相似文献
66.
ABA-regulated promoter activity in stomatal guard cells 总被引:4,自引:0,他引:4
Jane E. Taylor Kirstie F. Renwick Alex A.R. Webb Martin R. McAinsh Antonella Furini Dorothea Bartels Ralph S. Quatrano William R. Marcotte Jr. Alistair M. Hetherington 《The Plant journal : for cell and molecular biology》1995,7(1):129-134
CDeT6-19 is an ABA-regulated gene which has been isolated from Craterostigma plantagineum . The CDeT6-19 gene promoter has been fused to the β- glucuronidase reporter gene ( GUS ) and used to stably transform Arabidopsis thaliana and Nicotiana tabacum . This construct has been shown to be expressed in stomatal guard cells and often in the adjacent epidermal cells of both species in response to both exogenous ABA and drought stress. These results indicate that the stomatal guard cell is competent to relay an ABA signal to the nucleus. In contrast GUS expression directed by the promoter from a predominantly seed-specific, ABA-regulated gene, Em , or the promoter from the ABA-regulated CDeT27-45 gene is not detectable in the epidermal or guard cells of tobacco or Arabidopsis in response to ABA. The fact that not all ABA-regulated gene promoters are active in stomatal guard cells suggests that effective transduction of the signal is dependent upon particular regions within the gene promoter or that guard cells lack all or part of the specific transduction apparatus required to couple the ABA signal to these promoters. This suggests that there are multiple ABA stimulus response coupling pathways. The identification of a regulatory sequence from an ABA-induced gene which is expressed in stomatal guard cells creates the possibility of examining the role of Ca2+ and other second messengers in ABA-induced gene expression. 相似文献
67.
Alex J. Li Mindren Lu Israel Desta Vikram Sundar Gevorg Grigoryan Amy E. Keating 《Protein science : a publication of the Protein Society》2023,32(2)
Designing novel proteins to perform desired functions, such as binding or catalysis, is a major goal in synthetic biology. A variety of computational approaches can aid in this task. An energy‐based framework rooted in the sequence‐structure statistics of tertiary motifs (TERMs) can be used for sequence design on predefined backbones. Neural network models that use backbone coordinate‐derived features provide another way to design new proteins. In this work, we combine the two methods to make neural structure‐based models more suitable for protein design. Specifically, we supplement backbone‐coordinate features with TERM‐derived data, as inputs, and we generate energy functions as outputs. We present two architectures that generate Potts models over the sequence space: TERMinator, which uses both TERM‐based and coordinate‐based information, and COORDinator, which uses only coordinate‐based information. Using these two models, we demonstrate that TERMs can be utilized to improve native sequence recovery performance of neural models. Furthermore, we demonstrate that sequences designed by TERMinator are predicted to fold to their target structures by AlphaFold. Finally, we show that both TERMinator and COORDinator learn notions of energetics, and these methods can be fine‐tuned on experimental data to improve predictions. Our results suggest that using TERM‐based and coordinate‐based features together may be beneficial for protein design and that structure‐based neural models that produce Potts energy tables have utility for flexible applications in protein science. 相似文献
68.
Connor Brennan Adeeti Aggarwal Rui Pei David Sussillo Alex Proekt 《PLoS computational biology》2023,19(1)
The relationship between neuronal activity and computations embodied by it remains an open question. We develop a novel methodology that condenses observed neuronal activity into a quantitatively accurate, simple, and interpretable model and validate it on diverse systems and scales from single neurons in C. elegans to fMRI in humans. The model treats neuronal activity as collections of interlocking 1-dimensional trajectories. Despite their simplicity, these models accurately predict future neuronal activity and future decisions made by human participants. Moreover, the structure formed by interconnected trajectories—a scaffold—is closely related to the computational strategy of the system. We use these scaffolds to compare the computational strategy of primates and artificial systems trained on the same task to identify specific conditions under which the artificial agent learns the same strategy as the primate. The computational strategy extracted using our methodology predicts specific errors on novel stimuli. These results show that our methodology is a powerful tool for studying the relationship between computation and neuronal activity across diverse systems. 相似文献
69.
70.
Gonzalo Almanza Alex E. Clark Valentina Kouznetsova Eduardo Olmedillas Andrea Castro Igor F. Tsigelny Yan Wu George F. Gao Sandra L. Leibel William Bray Erica Ollmann Saphire Aaron F. Carlin Maurizio Zanetti 《PLoS pathogens》2022,18(7)
Successful control of the COVID-19 pandemic depends on vaccines that prevent transmission. The full-length Spike protein is highly immunogenic but the majority of antibodies do not target the virus: ACE2 interface. In an effort to affect the quality of the antibody response focusing it to the receptor-binding motif (RBM) we generated a series of conformationally-constrained immunogens by inserting solvent-exposed RBM amino acid residues into hypervariable loops of an immunoglobulin molecule. Priming C57BL/6 mice with plasmid (p)DNA encoding these constructs yielded a rapid memory response to booster immunization with recombinant Spike protein. Immune sera antibodies bound strongly to the purified receptor-binding domain (RBD) and Spike proteins. pDNA primed for a consistent response with antibodies efficient at neutralizing authentic WA1 virus and three variants of concern (VOC), B.1.351, B.1.617.2, and BA.1. We demonstrate that immunogens built on structure selection can be used to influence the quality of the antibody response by focusing it to a conserved site of vulnerability shared between wildtype virus and VOCs, resulting in neutralizing antibodies across variants. 相似文献