全文获取类型
收费全文 | 38610篇 |
免费 | 2495篇 |
国内免费 | 15篇 |
专业分类
41120篇 |
出版年
2023年 | 224篇 |
2022年 | 522篇 |
2021年 | 910篇 |
2020年 | 521篇 |
2019年 | 681篇 |
2018年 | 941篇 |
2017年 | 789篇 |
2016年 | 1317篇 |
2015年 | 2007篇 |
2014年 | 2148篇 |
2013年 | 2942篇 |
2012年 | 3376篇 |
2011年 | 3211篇 |
2010年 | 1956篇 |
2009年 | 1685篇 |
2008年 | 2396篇 |
2007年 | 2327篇 |
2006年 | 2059篇 |
2005年 | 1861篇 |
2004年 | 1752篇 |
2003年 | 1690篇 |
2002年 | 1521篇 |
2001年 | 307篇 |
2000年 | 209篇 |
1999年 | 297篇 |
1998年 | 379篇 |
1997年 | 256篇 |
1996年 | 252篇 |
1995年 | 231篇 |
1994年 | 225篇 |
1993年 | 222篇 |
1992年 | 136篇 |
1991年 | 148篇 |
1990年 | 147篇 |
1989年 | 109篇 |
1988年 | 101篇 |
1987年 | 90篇 |
1986年 | 70篇 |
1985年 | 96篇 |
1984年 | 95篇 |
1983年 | 72篇 |
1982年 | 84篇 |
1981年 | 81篇 |
1980年 | 80篇 |
1979年 | 73篇 |
1978年 | 39篇 |
1977年 | 50篇 |
1976年 | 37篇 |
1975年 | 39篇 |
1973年 | 42篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
Fernanda Augusta de Lima Barbosa Guterres Glaucia Regina MartinezMaria Eliane Merlin Rocha Sheila Maria Brochado Winnischofer 《Experimental cell research》2013
Recent studies demonstrated that simvastatin has antitumor properties in several types of cancer cells, mainly by inducing apoptosis and inhibiting growth. The arrest of proliferation is a feature of cellular senescence; however, the occurrence of senescence in melanoma cells upon simvastatin treatment has not been investigated until now. Our results demonstrated that exposure of human metastatic melanoma cells (WM9) to simvastatin induces a senescent phenotype, characterized by G1 arrest, positive staining for senescence-associated β-galactosidase assay, and morphological changes. Also, the main pathways leading to cell senescence were examined in simvastatin-treated human melanoma cells, and the expression levels of phospho-p53 and p21 were upregulated by simvastatin, suggesting that cell cycle regulators and DNA damage pathways are involved in the onset of senescence. Since simvastatin can act as a pro-oxidant agent, and oxidative stress may be related to senescence, we measured the intracellular ROS levels in WM9 cells upon simvastatin treatment. Interestingly, we found an increased amount of intracellular ROS in these cells, which was accompanied by elevated expression of catalase and peroxiredoxin-1. Collectively, our results demonstrated that simvastatin can induce senescence in human melanoma cells by activation of p53/p21 pathway, and that oxidative stress may be related to this process. 相似文献
962.
Theresa K. Hodges Kate L. Laskowski Giuseppe L. Squadrito Maria De Luca Jeff Leips 《Evolution; international journal of organic evolution》2013,67(3):749-760
Populations of Drosophila melanogaster face significant mortality risks from parasitoid wasps that use species‐specific strategies to locate and survive in hosts. We tested the hypothesis that parasitoids with different strategies select for alternative host defense characteristics and in doing so contribute to the maintenance of fitness variation and produce trade‐offs among traits. We characterized defense traits of Drosophila when exposed to parasitoids with different host searching behaviors (Aphaereta sp. and Leptopilina boulardi). We used host larvae with different natural alleles of the gene Dopa decarboxylase (Ddc), a gene controlling the production of dopamine and known to influence the immune response against parasitoids. Previous population genetic analyses indicate that our focal alleles are maintained by balancing selection. Genotypes exhibited a trade‐off between the immune response against Aphaereta sp. and the ability to avoid parasitism by L. boulardi. We also identified a trade‐off between the ability to avoid parasitism by L. boulardi and larval competitive ability as indicated by differences in foraging and feeding behavior. Genotypes differed in dopamine levels potentially explaining variation in these traits. Our results highlight the potential role of parasitoid biodiversity on host fitness variation and implicate Ddc as an antagonistic pleiotropic locus influencing larval fitness traits. 相似文献
963.
Isabella Daidone Massimiliano Aschi Maria Patamia Argante Bozzi Raffaele Petruzzelli 《Biopolymers》2013,99(1):47-54
Obtustatin and Lebestatin are lysine‐threonine‐serine (KTS)‐disintegrins, which are a family of low molecular weight polypeptides present in many viperidae venoms and are potent and specific inhibitors of collagen‐binding integrins. The integrin binding loop, harboring the 21KTS23 motif, and the C‐terminal tail are known to be responsible for the selective binding to the α1β1 integrin. Despite a very high sequence homology (only two mutations are present in Lebestatin relative to Obtustatin, namely R24L and S38L), Lebestatin exhibits a higher inhibitory effect than Obtustatin on cell adhesion and cell migration to collagens I and IV. Here we show, by means of molecular dynamics simulations of the two polypeptides in aqueous solution, that Lebestatin possesses a higher flexibility of the C‐terminal tail and a greater solvent accessibility of the integrin binding loop than Obtustatin. It may be hypothesized that these properties may contribute to the higher binding‐affinity of Lebestatin to its biological partner. © 2012 Wiley Periodicals, Inc. 相似文献
964.
Erich Y.T. Nakasu Simoni C. Dias Carmen S.S. Pires David A. Andow Debora Pires Paula Pedro Henrique B. Togni Tainã R. Macedo Edison R. Sujii Maria F.G. de Sá Eliana M.G. Fontes 《Entomologia Experimentalis et Applicata》2013,148(2):105-115
Insect predators are exposed to the Cry1Ac toxin in Bt cotton fields through several pathways. In this study, we investigated the effects of activated Cry1Ac added to a diet on Cycloneda sanguinea (L.) (Coleoptera: Coccinellidae), which is one of the main predators of non‐target pests in Brazilian cotton. Direct bitrophic exposure of C. sanguinea to Cry1Ac was done by feeding beetles with Aphis gossypii (Glover) (Hemiptera: Aphidae) sprayed with 500 μg per ml Cry1Ac solution. Larval and pupal survival, development time, aphid consumption, and adult longevity were recorded daily. Couples within the same experimental treatment were paired and numbers of eggs laid and hatched per female were recorded daily. Net replacement rate was calculated for each female. During development, a C. sanguinea larva consumed on average 1.8 μg of activated Cry1Ac. No significant differences due to Cry1Ac were observed for any of the response variables, except aphid consumption. Larvae receiving Cry1Ac consumed more aphids than larvae receiving distilled water alone. Additional statistical analyses were conducted to evaluate independence of responses, and for the independent responses, a simple meta‐analysis was conducted to test the null hypothesis that all responses were zero. Nearly all of the response variables were statistically independent. Two pairs of responses were not independent, but the associated multivariate tests were not significant. The meta‐analysis suggested that all effects were not different from random variation around zero and no cumulative effects could be detected. Our results indicated that bitrophic exposure to activated Cry1Ac is likely to have little or no adverse ecological effect on C. sanguinea. 相似文献
965.
Maria Regueiro Joseph Alvarez Diane Rowold Rene J. Herrera 《American journal of physical anthropology》2013,150(3):333-348
Given the importance of Y‐chromosome haplogroup Q to better understand the source populations of contemporary Native Americans, we studied 8 biallelic and 17 microsatellite polymorphisms on the background of 128 Q Y‐chromosomes from geographically targeted populations. The populations examined in this study include three from the Tuva Republic in Central Asia (Bai‐Tai, Kungurtug, and Toora‐Hem, n = 146), two from the northeastern tip of Siberia (New Chaplino and Chukchi, n = 32), and two from Mesoamerica (Mayans from Yucatan, Mexico n = 72, and Mayans from the Guatemalan Highlands, n = 43). We also see evidence of a dramatic Mesoamerican post‐migration population growth in the ubiquitous and diverse Y‐STR profiles of the Mayan and other Mesoamerican populations. In the case of the Mayans, this demographic growth was most likely fueled by the agricultural‐ and trade‐based subsistence adopted during the Pre‐Classic, Classic and Post‐Classic periods of their empire. The limited diversity levels observed in the Altaian and Tuvinian regions of Central Asia, the lowest of all populations examined, may be the consequence of bottleneck events fostered by the spatial isolation and low effective population size characteristic of a nomadic lifestyle. Furthermore, our data illustrate how a sociocultural characteristic such as mode of subsistence may be of impact on the genetic structure of populations. We analyzed our genetic data using Multidimensional Scaling Analysis of populations, Principal Component Analysis of individuals, Median‐joining networks of M242, M346, L54, and M3 individuals, age estimations based on microsatellite variation utilizing genealogical and evolutionary mutation rates/generation times and estimation of Y‐ STR average gene diversity indices. Am J Phys Anthropol, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
966.
The 16S rRNA gene has been used in the last decades as a gold standard for determining the phylogenetic position of bacteria and their taxonomy. It is a well conserved gene, with some variations, present in all bacteria and allows the reconstruction of genealogies of microorganisms. Nevertheless, this gene has its limitations when inferring phylogenetic relationships between closely related isolates. To overcome this problem, DNA–DNA hybridization appeared as a solution to clarify interspecies relationships when the sequence similarity of the 16S rRNA gene is above 97 %. However, this technique is time consuming, expensive and laborious and so, researchers developed other molecular markers such as sequencing of housekeeping or functional genes for accurate determination of bacterial phylogeny. One of these genes that have been used successfully, particularly in clinical microbiology, codes for the beta subunit of the RNA polymerase (rpoB). The rpoB gene is sufficiently conserved to be used as a molecular clock, it is present in all bacteria and it is a mono-copy gene. In this study, rpoB gene sequencing was applied to the phylum Planctomycetes. Based on the genomes of 19 planctomycetes it was possible to determine the correlation between the rpoB gene sequence and the phylogenetic position of the organisms at a 95–96 % sequence similarity threshold for a novel species. A 1200-bp fragment of the rpoB gene was amplified from several new planctomycetal isolates and their intra and inter-species relationships to other members of this group were determined based on a 96.3 % species border and 98.2 % for intraspecies resolution. 相似文献
967.
Olga Maria Lage 《Antonie van Leeuwenhoek》2013,104(4):499-508
During attempts to obtain axenic the cultures of the marine dinoflagellate Prorocentrum micans, a microorganism with peculiar features was isolated. This contaminant resisted the physical and antibiotic treatments performed. Subsequent characterization showed that in agar plates this microorganism develops round granular pink colonies. It is a salt-dependent mesophilic and chemoheterotrophic Gram negative bacterium with a rod to ovoid shape, presenting cell motility in young cultures. Cell division occurs by cell budding. The bacterium forms aggregates with a variable number of cells that are stacked by fibrillar glycoproteic material, the holdfast. A tuft of numerous short glycoproteic fimbriae emerges from one pole of the cell. Preeminent granular inclusions, also of glycoproteic nature, are present in the cytoplasm. Several structural and compositional aspects of the cell envelope and cytoplasm are provided. The production of fibrillar material and the existence of the polar appendages suggest that this microorganism should occur in aquatic environments bound to substrates and could be associated with P. micans in natural marine habitats. Based on the characteristics displayed, this microorganism is a member of the Planctomycetes, order Planctomycetales. 相似文献
968.
969.
Milagro Mottola Natalia Wilke Luciano Benedini Rafael Gustavo Oliveira Maria Laura Fanani 《生物化学与生物物理学报:生物膜》2013
Ascorbyl palmitate (ASC16) is an anionic amphiphilic molecule of pharmacological interest due to its antioxidant properties. We found that ASC16 strongly interacted with model membranes. ASC16 penetrated phospholipid monolayers, with a cutoff near the theoretical surface pressure limit. The presence of a lipid film at the interface favored ASC16 insertion compared with a bare air/water surface. The adsorption and penetration time curves showed a biphasic behavior: the first rapid peak evidenced a fast adsorption of charged ASC16 molecules to the interface that promoted a lowering of surface pH, thus partially neutralizing and compacting the film. The second rise represented an approach to the equilibrium between the ASC16 molecules in the subphase and the surface monolayer, whose kinetics depended on the ionization state of the film. Based on the Langmuir dimiristoylphosphatidylcholine + ASC16 monolayer data, we estimated an ASC16 partition coefficient to dimiristoylphosphatidylcholine monolayers of 1.5 × 105 and a ΔGp = − 6.7 kcal·mol− 1. The rheological properties of the host membrane were determinant for ASC16 penetration kinetics: a fluid membrane, as provided by cholesterol, disrupted the liquid-condensed ASC16-enriched domains and favored ASC16 penetration. Subphase pH conditions affected ASC16 aggregation in bulk: the smaller structures at acidic pHs showed a faster equilibrium with the surface film than large lamellar ones. Our results revealed that the ASC16 interaction with model membranes has a highly complex regulation. The polymorphism in the ASC16 bulk aggregation added complexity to the equilibrium between the surface and subphase form of ASC16, whose understanding may shed light on the pharmacological function of this drug. 相似文献
970.
Mario Venza Maria Visalli Teresa Catalano Cinzia Fortunato Rosaria Oteri Diana Teti Isabella Venza 《Biochemical and biophysical research communications》2013
Aberrant promoter methylation and resultant silencing of TRAIL decoy receptors were reported in a variety of cancers, but to date little is known about the relevance of this epigenetic modification in melanoma. In this study, we examined the methylation and the expression status of TRAIL receptor genes in cutaneous and uveal melanoma cell lines and specimens and their interaction with DNA methyltransferases (DNMTs) DNMT1, DNMT3a, and DNMT3b. DR4 and DR5 methylation was not frequent in cutaneous melanoma but on the contrary it was very frequent in uveal melanoma. No correlation between methylation status of DR4 and DR5 and gene expression was found. DcR1 and DcR2 were hypermethylated with very high frequency in both cutaneous and uveal melanoma. The concordance between methylation and loss of gene expression ranged from 91% to 97%. Here we showed that DNMT1 was crucial for DcR2 hypermethylation and that DNMT1 and DNMT3a coregulate the methylation status of DcR1. Our work also revealed the critical relevance of DcR1 and DcR2 expression in cell growth and apoptosis either in cutaneous or uveal melanoma. In conclusion, the results presented here claim for a relevant impact of aberrant methylation of decoy receptors in melanoma and allow to understand how the silencing of DcR1 and DcR2 is related to melanomagenesis. 相似文献