全文获取类型
收费全文 | 19626篇 |
免费 | 1726篇 |
国内免费 | 9篇 |
出版年
2023年 | 65篇 |
2022年 | 56篇 |
2021年 | 283篇 |
2020年 | 203篇 |
2019年 | 263篇 |
2018年 | 295篇 |
2017年 | 290篇 |
2016年 | 485篇 |
2015年 | 803篇 |
2014年 | 884篇 |
2013年 | 1098篇 |
2012年 | 1534篇 |
2011年 | 1587篇 |
2010年 | 977篇 |
2009年 | 843篇 |
2008年 | 1247篇 |
2007年 | 1305篇 |
2006年 | 1218篇 |
2005年 | 1197篇 |
2004年 | 1182篇 |
2003年 | 1096篇 |
2002年 | 1016篇 |
2001年 | 208篇 |
2000年 | 160篇 |
1999年 | 193篇 |
1998年 | 246篇 |
1997年 | 156篇 |
1996年 | 127篇 |
1995年 | 183篇 |
1994年 | 179篇 |
1993年 | 150篇 |
1992年 | 123篇 |
1991年 | 125篇 |
1990年 | 119篇 |
1989年 | 104篇 |
1988年 | 105篇 |
1987年 | 115篇 |
1986年 | 99篇 |
1985年 | 99篇 |
1984年 | 99篇 |
1983年 | 115篇 |
1982年 | 112篇 |
1981年 | 111篇 |
1980年 | 91篇 |
1979年 | 56篇 |
1978年 | 56篇 |
1977年 | 59篇 |
1976年 | 51篇 |
1975年 | 36篇 |
1974年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
61.
Sic L. Chan Steven P. Tammariello Steve Estus Mark P. Mattson 《Journal of neurochemistry》1999,73(2):502-512
Prostate apoptosis response-4 (Par-4) is the product of a gene up-regulated in prostate cancer cells undergoing apoptosis. We now report that Par-4 mRNA and protein levels rapidly and progressively increase 4-24 h following trophic factor withdrawal (TFW) in cultured embryonic rat hippocampal neurons. The increased Par-4 levels follow an increase of reactive oxygen species, and precede mitochondrial membrane depolarization, caspase activation, and nuclear chromatin condensation/fragmentation. Pretreatment of cultures with 17beta-estradiol, vitamin E, and uric acid largely prevented Par-4 induction and cell death following TFW, demonstrating necessary roles for oxidative stress and membrane lipid peroxidation in TFW-induced neuronal apoptosis. Par-4 antisense oligonucleotide treatment blocked Par-4 protein increases and attenuated mitochondrial dysfunction, caspase activation, and cell death following TFW. Collectively, our data identify Par-4 as an early and pivotal player in neuronal apoptosis resulting from TFW and suggest that estrogen and antioxidants may prevent apoptosis, in part, by suppressing Par-4 production. 相似文献
62.
C. Steven McDaniel Taghi Manshouri M. Zouhair Atassi 《Journal of Protein Chemistry》1987,6(5):455-461
A peptide corresponding to residues 26–41 of α-bungarotoxin, and closed by a disulfide bond between two cysteine residues
at the amino and C terminal ends of the peptide, was synthesized and the monomeric form was purified. The peptide, which represents
the exposed part of the long central loop of the toxin molecule, was examined for binding to acetylcholine receptor. The peptide
was shown by radiometric titrations to bind radiolabeled receptor, and radiolabeled peptide was bound by receptor. The specificity
of the binding was confirmed by inhibition with the parent toxin. A synthetic analog of the peptide in which Trp-28 was replaced
by glycine had very little (10%) of the original activity. Succinylation of the amino groups of the peptide resulted in virtually
complete (98%) loss of the binding activity. These results indicate that a shortened loop peptide corresponding to the region
26–41 of α-bungarotoxin exhibits binding activities mimicking those of the parent molecule. In this region, Trp-28, and one
or both of Lys-26 and Lys-38, are essential contact residues in the binding to receptor. 相似文献
63.
Marion S. R?der Mark E. Sorrells Steven D. Tanksley 《Molecular & general genetics : MGG》1992,232(2):215-220
Summary The long-range structure of 5S rRNA gene clusters has been investigated in wheat (Triticum aestivum L.) by means of pulsed field gel electrophoresis. Using aneuploid stocks, 5S rRNA gene clusters were assigned to sites on chromosomes 1B, 1D, 513 and 5D. Cluster sizes were evaluated and the copy number of 5S DNA repeats was estimated at 4700-5200 copies for the short repeating unit (410 bp) and about 3100 copies for the long repeat (500 bp) per haploid genome. A comparison of wheat cultivars revealed extremely high levels of polymorphism in the 5S rRNA gene clusters. With one restriction enzyme digest all varieties tested gave unique banding patterns and, on a per fragment basis, 21-fold more polymorphism was detected among cultivars for 5S DNA compared to standard restriction fragment length polymorphisms (RFLPs) detected with single copy clones. Experiments with aneuploid stocks suggest that the 5S rRNA gene clusters at several chromosomal sites contribute to this polymorphism. A number of previous reports have shown that wheat cultivars are not easily distinguished by isozymes or RFLPs. The high level of variation detected in 5S rRNA gene clusters therefore offers the possibility of a sensitive fingerprinting method for wheat. 5S DNA and other macro-satellite sequences may also serve as hypervariable Mendelian markers for genetic and breeding experiments in wheat. 相似文献
64.
Steven L. Gonias Salvatore V. Pizzo 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,678(2):268-274
Clearance studies were performed in mice using α2-macroglobulin (α2M), α2M-trypsin comlex and α2M-CH3NH2 complex. All three species were incubated with cis-dichlorodiamine platinum(II) (cis-DDPt) at concentrations between 9.0 μM and 1.67 mM for 4 h and then dialyzed. The clearance rate of native α2M was unchanged following incubation with cis-DDPt. α2M-trypsin and α2M-CH3NH2 cleared rapidly from the ciruculation; however, reaction with cis-DDPt significantly decreased the plasma elimination rate of both complexes. Non-denaturing gel electrophoresis and α2M activity assays demonstrated relative stability following incubations with cis-DDPt which markedly altered clearance. Evidence for cis-DDPt crosslinking of α2M subunits was obtained: however, whether this crosslinking is involved in altered clearance remains undetermined. Iodoacetamide treatment of α2M did not duplicate the effect of cis-DDPton α2M clearance, nor did it inhibit the effect of cis-DDPt on α2M clearance. Plasma elimination of α2M complex was also unaltered by pretreatment of mice with intravenous free cis-DDPt. 相似文献
65.
Germination and Emergence of Primed Grass Seeds Under Field and Simulated-field Temperature Regimes 总被引:5,自引:4,他引:1
Seed priming may enhance establishment success of cool-seasonrange grasses which must compete with annual weeds for earlyspring moisture. Previous priming studies have confirmed germinationrate enhancement for these species but relative treatment effectsunder field-temperature conditions have not been assessed. Weprimed seeds of thickspike wheatgrass [Elymus lanceolatus(Scribn.and J. G. Smith) Gould], bluebunch wheatgrass [Pseudoroegneriaspicata(Pursh) Löve], Sandberg bluegrass (Poa sandbergiiVasey.) and bottlebrush squirreltail [Elymus elymoides(Raf.)Swezey] and evaluated their relative emergence rate in threesoil types as a function of spring-planting date. Germinationresponse was simultaneously evaluated in laboratory germinatorsthat were programmed to simulate the field-temperature regimeat planting depth. Seed priming enhanced both germination andemergence rate with the greatest effect occurring during theearlier, cooler planting dates. Total emergence and emergencerate in the field were lower than for the equivalent germinationresponse in the laboratory. Thermal-germination response wasmodelled and predictions developed for evaluating potentialgermination under late winter/early spring soil-temperatureregimes. Modelling results predicted that greater germinationenhancement would have been possible at earlier planting datesthan were measured in the field experiment.Copyright 2000 Annalsof Botany Company Bunchgrass, germination, emergence, priming, rate, temperature 相似文献
66.
67.
68.
Data assimilation is a valuable tool in the study of any complex system, where measurements are incomplete, uncertain, or both. It enables the user to take advantage of all available information including experimental measurements and short-term model forecasts of a system. Although data assimilation has been used to study other biological systems, the study of the sleep-wake regulatory network has yet to benefit from this toolset. We present a data assimilation framework based on the unscented Kalman filter (UKF) for combining sparse measurements together with a relatively high-dimensional nonlinear computational model to estimate the state of a model of the sleep-wake regulatory system. We demonstrate with simulation studies that a few noisy variables can be used to accurately reconstruct the remaining hidden variables. We introduce a metric for ranking relative partial observability of computational models, within the UKF framework, that allows us to choose the optimal variables for measurement and also provides a methodology for optimizing framework parameters such as UKF covariance inflation. In addition, we demonstrate a parameter estimation method that allows us to track non-stationary model parameters and accommodate slow dynamics not included in the UKF filter model. Finally, we show that we can even use observed discretized sleep-state, which is not one of the model variables, to reconstruct model state and estimate unknown parameters. Sleep is implicated in many neurological disorders from epilepsy to schizophrenia, but simultaneous observation of the many brain components that regulate this behavior is difficult. We anticipate that this data assimilation framework will enable better understanding of the detailed interactions governing sleep and wake behavior and provide for better, more targeted, therapies. 相似文献
69.
Justin Mancini Brooke Weckselblatt Yoonjie K. Chung Julia C. Durante Steven Andelman Jessica Glaubman Justin D. Dorff Samhita Bhargava Rebeccah S. Lijek Katherine P. Unger Iruka N. Okeke 《Journal of bacteriology》2011,193(18):4813-4820
Heat-resistant agglutinin 1 (Hra1) is an accessory colonization factor of enteroaggregative Escherichia coli (EAEC) strain 042. Tia, a close homolog of Hra1, is an invasin and adhesin that has been described in enterotoxigenic E. coli. We devised a PCR-restriction fragment length polymorphism screen for the associated genes and found that they occur among 55 (36.7%) of the enteroaggregative E. coli isolates screened, as well as lower proportions of enterotoxigenic, enteropathogenic, enterohemorrhagic, and commensal E. coli isolates. Overall, 25%, 8%, and 3% of 150 EAEC strains harbored hra1 alone, tia alone, or both genes, respectively. One EAEC isolate, 60A, produced an amplicon with a unique restriction profile, distinct from those of hra1 and tia. We cloned and sequenced the full-length agglutinin gene from strain 60A and have designated it hra2. The hra2 gene was not detected in any of 257 diarrheagenic E. coli isolates in our collection but is present in the genome of Salmonella enterica serovar Heidelberg strain SL476. The cloned hra2 gene from strain 60A, which encodes a predicted amino acid sequence that is 64% identical to that of Hra1 and 68% identical to that of Tia, was sufficient to confer adherence on E. coli K-12. We constructed an hra2 deletion mutant of EAEC strain 60A. The mutant was deficient in adherence but not autoaggregation or invasion, pointing to a functional distinction from the autoagglutinin Hra1 and the Tia invasin. Hra1, Tia, and the novel accessory adhesin Hra2 are members of a family of integral outer membrane proteins that confer different colonization-associated phenotypes. 相似文献
70.
Steven I. Higgins Robert B. O’Hara Olga Bykova Michael D. Cramer Isabelle Chuine Eva‐Maria Gerstner Thomas Hickler Xavier Morin Michael R. Kearney Guy F. Midgley Simon Scheiter 《Journal of Biogeography》2012,39(12):2132-2145
Aim To develop a physiologically based model of the plant niche for use in species distribution modelling. Location Europe. Methods We link the Thornley transport resistance (TTR) model with functions which describe how the TTR’s model parameters are influenced by abiotic environmental factors. The TTR model considers how carbon and nutrient uptake, and the allocation of these assimilates, influence growth. We use indirect statistical methods to estimate the model parameters from a high resolution data set on tree distribution for 22 European tree species. Results We infer, from distribution data and abiotic forcing data, the physiological niche dimensions of 22 European tree species. We found that the model fits were reasonable (AUC: 0.79–0.964). The projected distributions were characterized by a false positive rate of 0.19 and a false negative rate 0.12. The fitted models are used to generate projections of the environmental factors that limit the range boundaries of the study species. Main conclusions We show that physiological models can be used to derive physiological niche dimensions from species distribution data. Future work should focus on including prior information on physiological rates into the parameter estimation process. Application of the TTR model to species distribution modelling suggests new avenues for establishing explicit links between distribution and physiology, and for generating hypotheses about how ecophysiological processes influence the distribution of plants. 相似文献