全文获取类型
收费全文 | 1975篇 |
免费 | 157篇 |
专业分类
2132篇 |
出版年
2024年 | 4篇 |
2023年 | 8篇 |
2022年 | 26篇 |
2021年 | 36篇 |
2020年 | 25篇 |
2019年 | 37篇 |
2018年 | 38篇 |
2017年 | 38篇 |
2016年 | 66篇 |
2015年 | 96篇 |
2014年 | 94篇 |
2013年 | 149篇 |
2012年 | 158篇 |
2011年 | 162篇 |
2010年 | 95篇 |
2009年 | 83篇 |
2008年 | 120篇 |
2007年 | 132篇 |
2006年 | 126篇 |
2005年 | 117篇 |
2004年 | 105篇 |
2003年 | 109篇 |
2002年 | 100篇 |
2001年 | 15篇 |
2000年 | 14篇 |
1999年 | 18篇 |
1998年 | 19篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 10篇 |
1994年 | 12篇 |
1993年 | 15篇 |
1992年 | 10篇 |
1991年 | 11篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 8篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有2132条查询结果,搜索用时 0 毫秒
991.
Berger D Dutia M Powell D Wissner A DeMorin F Raifeld Y Weber J Boschelli F 《Bioorganic & medicinal chemistry letters》2002,12(20):2989-2992
A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitors of Src kinase, and have potent activity against Src-transformed fibroblast cells. 相似文献
992.
Sitnikova Tatiana Ya. Naumova Tatiana V. Mekhanikova Irina V. Kiyashko Sergey I. Kalmychkov Gennady V. Karanovic Ivana Zakharenko Alexandra S. Bukin Yuri S. Khabuev Andrey V. Ivanov Vyacheslav G. Khlystov Oleg M. Zemskaya Tamara I. 《Hydrobiologia》2022,849(8):1947-1968
Hydrobiologia - The biological traits of invertebrates inhabiting freshwater methane seeps are poorly understood. We analysed the relationship between invertebrate abundance and environmental... 相似文献
993.
Genome trees and the tree of life 总被引:16,自引:0,他引:16
Genome comparisons indicate that horizontal gene transfer and differential gene loss are major evolutionary phenomena that, at least in prokaryotes, involve a large fraction, if not the majority, of genes. The extent of these events casts doubt on the feasibility of constructing a 'Tree of Life', because the trees for different genes often tell different stories. However, alternative approaches to tree construction that attempt to determine tree topology on the basis of comparisons of complete gene sets seem to reveal a phylogenetic signal that supports the three-domain evolutionary scenario and suggests the possibility of delineation of previously undetected major clades of prokaryotes. If the validity of these whole-genome approaches to tree building is confirmed by analyses of numerous new genomes, which are currently being sequenced at an increasing rate, it would seem that the concept of a universal 'species' tree is still appropriate. However, this tree should be reinterpreted as a prevailing trend in the evolution of genome-scale gene sets rather than as a complete picture of evolution. 相似文献
994.
A new genus and species of Discocephalini, Acanthocephalonotum martinsnetoi
gen. n. et sp. n. is described from Río Pichileufú, middle Eocene of Patagonia, Argentina at palaeolatitude ~ 46°S. The new species is the first fossil representative of the Discocephalinae. This taxon is extant in equatorial to subtropical America, and some species reach warm temperate latitudes (Buenos Aires province). The new genus is distinguished from the other genera of Discocephalini by the combination of these characters: interocular width greater than head length; head massive and quadrangular with the anterior margin almost straight; juga touching each other; labrum thick and curved; triangular ante-ocular process extending beyond the eye; broad spine-like antero-lateral process of the pronotum; pronotum explanate and bean shaped; scutellum triangular with a circular tongue reaching the anterior side of abdominal segment 7; and wings well developed with membrane just surpassing end of abdomen. 相似文献
995.
Flávio O. Francisco Leandro R. Santiago Yuri M. Mizusawa Benjamin P. Oldroyd Maria C. Arias 《Journal of Insect Conservation》2016,20(3):383-394
As a consequence of founder effects, small population size and demographic constraints, island populations are often characterized by low genetic diversity and high inbreeding. The effects of inbreeding are more pronounced in haplo-diploid insects like bees than in similar diploid species, because their method of sex determination requires heterozygosity at a sex locus. Inbreeding leads to homozygosity at the sex locus and the production of non-viable diploid males. This means that island populations of bees are particularly prone to extinction. Here we determine the levels of diversity and isolation between islands and mainland populations of the bumble bee Bombus morio in southeast Brazil. We analyzed 659 individuals from 24 populations, sequencing two mitochondrial genes (COI and Cytb) and genotyping all individuals at 14 microsatellite loci. Surprisingly, genetic diversity was high and genetic isolation was low in all populations except Teodoro Sampaio (mainland) and Ilha da Vitória (island). Genetic diversity is not significantly correlated with island area, but is lower in populations that are more distant from the mainland. Except perhaps for Ilha da Vitória, we suggest that the island populations are unlikely to go extinct due to genetic factors. Finally, based on its genetic distance from all other populations, we identify a putative new subspecies in the Teodoro Sampaio region. 相似文献
996.
Iwakawa HO Tajima Y Taniguchi T Kaido M Mise K Tomari Y Taniguchi H Okuno T 《Journal of virology》2012,86(15):7836-7849
Viruses employ an alternative translation mechanism to exploit cellular resources at the expense of host mRNAs and to allow preferential translation. Plant RNA viruses often lack both a 5' cap and a 3' poly(A) tail in their genomic RNAs. Instead, cap-independent translation enhancer elements (CITEs) located in the 3' untranslated region (UTR) mediate their translation. Although eukaryotic translation initiation factors (eIFs) or ribosomes have been shown to bind to the 3'CITEs, our knowledge is still limited for the mechanism, especially for cellular factors. Here, we searched for cellular factors that stimulate the 3'CITE-mediated translation of Red clover necrotic mosaic virus (RCNMV) RNA1 using RNA aptamer-based one-step affinity chromatography, followed by mass spectrometry analysis. We identified the poly(A)-binding protein (PABP) as one of the key players in the 3'CITE-mediated translation of RCNMV RNA1. We found that PABP binds to an A-rich sequence (ARS) in the viral 3' UTR. The ARS is conserved among dianthoviruses. Mutagenesis and a tethering assay revealed that the PABP-ARS interaction stimulates 3'CITE-mediated translation of RCNMV RNA1. We also found that both the ARS and 3'CITE are important for the recruitment of the plant eIF4F and eIFiso4F factors to the 3' UTR and of the 40S ribosomal subunit to the viral mRNA. Our results suggest that dianthoviruses have evolved the ARS and 3'CITE as substitutes for the 3' poly(A) tail and the 5' cap of eukaryotic mRNAs for the efficient recruitment of eIFs, PABP, and ribosomes to the uncapped/nonpolyadenylated viral mRNA. 相似文献
997.
Salone B Martina Y Piersanti S Cundari E Cherubini G Franqueville L Failla CM Boulanger P Saggio I 《Journal of virology》2003,77(24):13448-13454
Many adenovirus serotypes enter cells by high-affinity binding to the coxsackievirus-adenovirus receptor (CAR) and integrin-mediated internalization. In the present study, we analyzed the possible receptor function of α3β1 for adenovirus serotype 5 (Ad5). We found that penton base and integrin α3β1 could interact in vitro. In vivo, both Ad5-cell binding and virus-mediated transduction were inhibited in the presence of anti-α3 and anti-β1 function-blocking antibodies, and this occurred in both CAR-positive and CAR-negative cell lines. Peptide library screenings and data from binding experiments with wild-type and mutant penton base proteins suggest that the Arg-Gly-Asp (RGD) in the penton base protein, the best known integrin binding motif, is only part of the binding interface with α3β1, which involved multiple additional contact sites. 相似文献
998.
Eu-heterochromatic rearrangements induce replication of heterochromatic sequences normally underreplicated in polytene chromosomes of Drosophila melanogaster 下载免费PDF全文
Abramov YA Kogan GL Tolchkov EV Rasheva VI Lavrov SA Bonaccorsi S Kramerova IA Gvozdev VA 《Genetics》2005,171(4):1673-1681
In polytene chromosomes of D. melanogaster the heterochromatic pericentric regions are underreplicated (underrepresented). In this report, we analyze the effects of eu-heterochromatic rearrangements involving a cluster of the X-linked heterochromatic (Xh) Stellate repeats on the representation of these sequences in salivary gland polytene chromosomes. The discontinuous heterochromatic Stellate cluster contains specific restriction fragments that were mapped along the distal region of Xh. We found that transposition of a fragment of the Stellate cluster into euchromatin resulted in its replication in polytene chromosomes. Interestingly, only the Stellate repeats that remain within the pericentric Xh and are close to a new eu-heterochromatic boundary were replicated, strongly suggesting the existence of a spreading effect exerted by the adjacent euchromatin. Internal rearrangements of the distal Xh did not affect Stellate polytenization. We also demonstrated trans effects exerted by heterochromatic blocks on the replication of the rearranged heterochromatin; replication of transposed Stellate sequences was suppressed by a deletion of Xh and restored by addition of Y heterochromatin. This phenomenon is discussed in light of a possible role of heterochromatic proteins in the process of heterochromatin underrepresentation in polytene chromosomes. 相似文献
999.
Oculocutaneous albinism type 1: link between mutations,tyrosinase conformational stability,and enzymatic activity 下载免费PDF全文
Monika B. Dolinska Nicole J. Kus S. Katie Farney Paul T. Wingfield Brian P. Brooks Yuri V. Sergeev 《Pigment cell & melanoma research》2017,30(1):41-52
Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of OCA1 have been described: severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes of OCA1 patients. Proteins were prepared using site‐directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. The OCA1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimicking OCA1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates that OCA1A mutations inactivate tyrosinase and result in severe phenotype, while OCA1B mutations partially inactivate tyrosinase and result in OCA1B albinism. 相似文献
1000.
Christopher L. Cioffi Mark A. Wolf Peter R. Guzzo Kashinath Sadalapure Visweswaran Parthasarathy Dattatraya Dethe Jun-Ho Maeng Edmund Carulli David T.J. Loong Xiao Fang Min Hu Priya Gupta Mark Chung Mei Bai Nick Moore Michele Luche Yuri Khmelnitsky Patrick L. Love Shuang Liu 《Bioorganic & medicinal chemistry letters》2013,23(5):1257-1261
The design, synthesis, and structure–activity relationships (SAR) of a series of N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1) are described. Optimization of the benzamide and central ring components of the core scaffold led to the identification of a GlyT-1 inhibitor that demonstrated in vivo activity in a rodent cerebral spinal fluid (CSF) glycine model. 相似文献