全文获取类型
收费全文 | 16256篇 |
免费 | 1683篇 |
国内免费 | 2篇 |
专业分类
17941篇 |
出版年
2022年 | 155篇 |
2021年 | 267篇 |
2020年 | 161篇 |
2019年 | 189篇 |
2018年 | 217篇 |
2017年 | 194篇 |
2016年 | 333篇 |
2015年 | 515篇 |
2014年 | 630篇 |
2013年 | 793篇 |
2012年 | 905篇 |
2011年 | 871篇 |
2010年 | 554篇 |
2009年 | 443篇 |
2008年 | 642篇 |
2007年 | 708篇 |
2006年 | 600篇 |
2005年 | 625篇 |
2004年 | 590篇 |
2003年 | 497篇 |
2002年 | 528篇 |
2001年 | 432篇 |
2000年 | 420篇 |
1999年 | 357篇 |
1998年 | 192篇 |
1997年 | 164篇 |
1996年 | 156篇 |
1995年 | 134篇 |
1994年 | 155篇 |
1993年 | 142篇 |
1992年 | 255篇 |
1991年 | 247篇 |
1990年 | 254篇 |
1989年 | 233篇 |
1988年 | 233篇 |
1987年 | 253篇 |
1986年 | 198篇 |
1985年 | 214篇 |
1984年 | 196篇 |
1983年 | 187篇 |
1982年 | 154篇 |
1981年 | 146篇 |
1980年 | 137篇 |
1979年 | 188篇 |
1978年 | 184篇 |
1977年 | 141篇 |
1976年 | 137篇 |
1975年 | 144篇 |
1974年 | 149篇 |
1972年 | 152篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Camille Szmaragd Anthony J. Wilson Simon Carpenter James L. N. Wood Philip S. Mellor Simon Gubbins 《PloS one》2009,4(11)
Background
Recently much attention has been given to developing national-scale micro-simulation models for livestock diseases that can be used to predict spread and assess the impact of control measures. The focus of these models has been on directly transmitted infections with little attention given to vector-borne diseases such as bluetongue, a viral disease of ruminants transmitted by Culicoides biting midges. Yet BT has emerged over the past decade as one of the most important diseases of livestock.Methodology/Principal Findings
We developed a stochastic, spatially-explicit, farm-level model to describe the spread of bluetongue virus (BTV) within and between farms. Transmission between farms was modeled by a generic kernel, which includes both animal and vector movements. Once a farm acquired infection, the within-farm dynamics were simulated based on the number of cattle and sheep kept on the farm and on local temperatures. Parameter estimates were derived from the published literature and using data from the outbreak of bluetongue in northern Europe in 2006. The model was validated using data on the spread of BTV in Great Britain during 2007. The sensitivity of model predictions to the shape of the transmission kernel was assessed.Conclusions/Significance
The model is able to replicate the dynamics of BTV in Great Britain. Although uncertainty remains over the precise shape of the transmission kernel and certain aspects of the vector, the modeling approach we develop constitutes an ideal framework in which to incorporate these aspects as more and better data become available. Moreover, the model provides a tool with which to examine scenarios for the spread and control of BTV in Great Britain. 相似文献992.
Preethi Ramachandran Romina Barria James Ashley Vivian Budnik 《Developmental neurobiology》2009,69(9):583-602
Actin remodeling has emerged as a critical process during synapse development and plasticity. Thus, understanding the regulatory mechanisms controlling actin organization at synapses is exceedingly important. Here, we used the highly plastic Drosophila neuromuscular junction (NMJ) to understand mechanisms of actin remodeling at postsynaptic sites. Previous studies have suggested that the actin‐binding proteins Spectrin and Coracle play a critical role in NMJ development and the anchoring of glutamate receptors most likely through actin regulation. Here, we show that an additional determinant of actin organization at the postsynaptic region is the PDZ protein Baz/Par‐3. Decreasing Baz levels in postsynaptic muscles has dramatic consequences for the size of F‐actin and spectrin domains at the postsynaptic region. In turn, proper localization of Baz at this site depends on both phosphorylation and dephosphorylation events. Baz phosphorylation by its binding partner, atypical protein kinase C (aPKC), is required for normal Baz targeting to the postsynaptic region. However, the retention of Baz at this site depends on its dephosphorylation mediated by the lipid and protein phosphatase PTEN. Misregulation of the phosphorylation state of Baz by genetic alterations in PTEN or aPKC activity has detrimental consequences for postsynaptic F‐actin and spectrin localization, synaptic growth, and receptor localization. Our results provide a novel mechanism of postsynaptic actin regulation through Baz, governed by the antagonistic actions of aPKC and PTEN. Given the conservation of these proteins from worms to mammals, these results are likely to provide new insight into actin organization pathways. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 相似文献
993.
The yeast GLC7 gene required for glycogen accumulation encodes a type 1 protein phosphatase. 总被引:10,自引:0,他引:10
Z H Feng S E Wilson Z Y Peng K K Schlender E M Reimann R J Trumbly 《The Journal of biological chemistry》1991,266(35):23796-23801
The glc7 mutant of the yeast Saccharomyces cerevisiae does not accumulate glycogen due to a defect in glycogen synthase activation (Peng, Z., Trumbly, R. J., and Reimann, E.M. (1990) J. Biol. Chem. 265, 13871-13877) whereas wild-type strains accumulate glycogen as the cell cultures approach stationary phase. We isolated the GLC7 gene by complementation of the defect in glycogen accumulation and found that the GLC7 gene is the same as the DIS2S1 gene (Ohkura, H., Kinoshita, N., Miyatani, S., Toda, T., and Yanagida, M. (1989) Cell 57, 997-1007). The protein product predicted by the GLC7 DNA sequence has a sequence that is 81% identical with rabbit protein phosphatase 1 catalytic subunit. Protein phosphatase 1 activity was greatly diminished in extracts from glc7 mutant cells. Two forms of protein phosphatase 1 were identified after chromatography of extracts on DEAE-cellulose. Both forms were diminished in the glc7 mutant and were partly restored by transformation with a plasmid carrying the GLC7 gene. Southern blots indicate the presence of a single copy of GLC7 in S. cerevisiae, and gene disruption experiments showed that the GLC7 gene is essential for cell viability. The GLC7 mRNA was identified as a 1.4-kilobase RNA that increases 4-fold at the end of exponential growth in wild-type cells, suggesting that activation of glycogen synthase is mediated by increased expression of protein phosphatase 1 as cells reach stationary phase. 相似文献
994.
John G Hodgson Gabriel Montserrat Marti Bozena er Glynis Jones Amy Bogaard Mike Charles Xavier Font Mohammed Ater Abdelkader Taleb Bianca A Santini Younes Hmimsa Carol Palmer Peter J Wilson Stuart R Band Amy Styring Charlotte Diffey Laura Green Erika Nitsch Elizabeth Stroud Gemma Warham 《Annals of botany》2020,126(7):1109
Background and AimsPlants depend fundamentally on establishment from seed. However, protocols in trait-based ecology currently estimate seed size but not seed number. This can be rectified. For annuals, seed number should simply be a positive function of vegetative biomass and a negative function of seed size.MethodsUsing published values of comparative seed number as the ‘gold standard’ and a large functional database, comparative seed yield and number per plant and per m2 were predicted by multiple regression. Subsequently, ecological variation in each was explored for English and Spanish habitats, newly calculated C-S-R strategies and changed abundance in the British flora.Key ResultsAs predicted, comparative seed mass yield per plant was consistently a positive function of plant size and competitive ability, and largely independent of seed size. Regressions estimating comparative seed number included, additionally, seed size as a negative function. Relationships differed numerically between regions, habitats and C-S-R strategies. Moreover, some species differed in life history over their geographical range. Comparative seed yield per m2 was positively correlated with FAO crop yield, and increasing British annuals produced numerous seeds. Nevertheless, predicted values must be viewed as comparative rather than absolute: they varied according to the ‘gold standard’ predictor used. Moreover, regressions estimating comparative seed yield per m2 achieved low precision.ConclusionsFor the first time, estimates of comparative seed yield and number for >800 annuals and their predictor equations have been produced and the ecological importance of these regenerative traits has been illustrated. ‘Regenerative trait-based ecology’ remains in its infancy, with work needed on determinate vs. indeterminate flowering (‘bet-hedging’), C-S-R methodologies, phylogeny, comparative seed yield per m2 and changing life history. Nevertheless, this has been a positive start and readers are invited to use estimates for >800 annuals, in the Supplementary data, to help advance ‘regenerative trait-based ecology’ to the next level. 相似文献
995.
Various age-related diseases increase in incidence during perimenopause. However, our understanding of the effects of aging compared with hormonal changes of perimenopause in mediating these disease risks is incomplete, in part due to the lack of an experimental perimenopause model. We therefore aimed to determine whether manipulation of the transition to ovarian failure in rats via the use of 4-vinylcyclohexene diepoxide (VCD) could be used to model and accelerate hormonal changes characteristic of perimenopause. We examined long-term (11 to 20 mo), dose-dependent effects of VCD on reproductive function in 1- and 3-mo-old female Sprague-Dawley rats. Twenty-five daily doses of VCD (80 or 160 mg/kg daily compared with vehicle alone) depleted ovarian follicles in a dose-dependent fashion in rats of both ages, accelerated the onset of acyclicity, and caused dose-dependent increases in follicle-stimulating hormone that exceeded those naturally occurring with age in control rats but left serum levels of 17β-estradiol unchanged, with continued ovarian production of androstenedione. High-dose VCD caused considerable nonovarian toxicities in 3-mo-old Sprague-Dawley rats, making this an unsuitable model. In contrast, 1-mo-old rats had more robust dose-dependent increases in follicle-stimulating hormone without evidence of systemic toxicity in response to either VCD dose. Because perimenopause is characterized by an increase in follicle-stimulating hormone with continued secretion of ovarian steroids, VCD acceleration of an analogous hormonal milieu in 1-mo-old Sprague-Dawley rats may be useful for probing the hormonal effects of perimenopause on age-related disease risk. 相似文献
996.
mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species 总被引:4,自引:0,他引:4
Reconstructions of the human-African great ape phylogeny by using
mitochondrial DNA (mtDNA) have been subject to considerable debate. One
confounding factor may be the lack of data on intraspecific variation. To
test this hypothesis, we examined the effect of intraspecific mtDNA
diversity on the phylogenetic reconstruction of another Plio- Pleistocene
radiation of higher primates, the fascicularis group of macaque (Macaca)
monkey species. Fifteen endonucleases were used to identify 10 haplotypes
of 40-47 restriction sites in M. mulatta, which were compared with similar
data for the other members of this species group. Interpopulational,
intraspecific mtDNA diversity was large (0.5%- 4.5%), and estimates of
divergence time and branching order incorporating this variation were
substantially different from those based on single representatives of each
species. We conclude that intraspecific mtDNA diversity is substantial in
at least some primate species. Consequently, without prior information on
the extent of genetic diversity within a particular species, intraspecific
variation must be assessed and accounted for when reconstructing primate
phylogenies. Further, we question the reliability of hominoid mtDNA
phylogenies, based as they are on one or a few representatives of each
species, in an already depauperate superfamily of primates.
相似文献
997.
James R. Stewart Ashley N. Mathieson Tom W. Ecay Jacquie F. Herbert Scott L. Parker Michael B. Thompson 《Journal of morphology》2010,271(11):1342-1351
The eggshell of lizards is a complex structure composed of organic and inorganic molecules secreted by the oviduct, which protects the embryo by providing a barrier to the external environment and also allows the exchange of respiratory gases and water for life support. Calcium deposited on the surface of the eggshell provides an important nutrient source for the embryo. Variation in physical conditions encountered by eggs results in a tradeoff among these functions and influences eggshell structure. Evolution of prolonged uterine egg retention results in a significant change in the incubation environment, notably reduction in efficiency of gas exchange, and selection should favor a concomitant reduction in eggshell thickness. This model is supported by studies that demonstrate an inverse correlation between eggshell thickness and length of uterine egg retention. One mechanism leading to thinning of the eggshell is reduction in size of uterine shell glands. Saiphos equalis is an Australian scincid lizard with an unusual pattern of geographic variation in reproductive mode. All populations retain eggs in the uterus beyond the embryonic stage at oviposition typical for lizards, and some are viviparous. We compared structure and histochemistry of the uterus and eggshell of two populations of S. equalis, prolonged egg retention, and viviparous to test the hypotheses: 1) eggshell thickness is inversely correlated with length of egg retention and 2) eggshell thickness is positively correlated with size of shell glands. We found support for the first hypothesis but also found that eggshells of both populations are surprisingly thick compared with other lizards. Our histochemical data support prior conclusions that uterine shell glands are the source of protein fiber matrix of the eggshell, but we did not find a correlation between size of shell glands and eggshell thickness. Eggshell thickness is likely determined by density of uterine shell glands in this species. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc. 相似文献
998.
Electric toothbrushes were evaluated using a model of plaque removal by fluid shear forces. Sucrose supplementation during plaque development did not affect the removal of bacteria from biofilm exposed to low-energy shear but did increase their resistance to high-energy shear. The toothbrush supplying high-energy shear forces removed significantly more viable bacteria. 相似文献
999.
Regulation of yeast glycogen phosphorylase by the cyclin-dependent protein kinase Pho85p 总被引:3,自引:0,他引:3
Yeast accumulate glycogen in response to nutrient limitation. The key enzymes of glycogen synthesis and degradation, glycogen synthase, and phosphorylase, are regulated by reversible phosphorylation. Phosphorylation inactivates glycogen synthase but activates phosphorylase. The kinases and phosphatases that control glycogen synthase are well characterized whilst the enzymes modifying phosphorylase are poorly defined. Here, we show that the cyclin-dependent protein kinase, Pho85p, which we have previously found to regulate glycogen synthase also controls the phosphorylation state of phosphorylase. 相似文献
1000.
Moroz OV Murzin AG Makarova KS Koonin EV Wilson KS Galperin MY 《Journal of molecular biology》2005,347(2):243-255
Structure-guided analysis of the new dimeric dUTPase family revealed its sequence relationship to the phage T4 dCTPase, phosphoribosyl-ATP pyrophosphatase HisE, NTP pyrophosphatase MazG, and several uncharacterized protein families, including the human protein XTP3TPA (RS21-C6), which is overexpressed in embryonic and cancer cells. Comparison with the recently determined structure of a MazG-like protein from Sulfolobus solfataricus supported the unification of these enzymes in one superfamily of all-alpha NTP pyrophosphatases, suggesting that dimeric dUTPases evolved from a tetrameric MazG-like ancestor by gene duplication. Analysis of the structure of the Sulfolobus MazG points to 2-hydroxyadenosine (isoguanosine) triphosphate, a product of oxidative damage of ATP, as the most likely substrate. We predict that uncharacterized members of this superfamily perform "house-cleaning" functions by hydrolyzing abnormal NTPs and are functionally analogous to the structurally unrelated hydrolases of the Nudix superfamily. We outline probable tertiary and quaternary structures of the all-alpha NTP pyrophosphatase superfamily members. 相似文献