全文获取类型
收费全文 | 6928篇 |
免费 | 685篇 |
国内免费 | 1篇 |
出版年
2023年 | 25篇 |
2022年 | 60篇 |
2021年 | 110篇 |
2020年 | 75篇 |
2019年 | 95篇 |
2018年 | 98篇 |
2017年 | 118篇 |
2016年 | 168篇 |
2015年 | 270篇 |
2014年 | 321篇 |
2013年 | 363篇 |
2012年 | 433篇 |
2011年 | 454篇 |
2010年 | 311篇 |
2009年 | 276篇 |
2008年 | 342篇 |
2007年 | 358篇 |
2006年 | 290篇 |
2005年 | 321篇 |
2004年 | 332篇 |
2003年 | 329篇 |
2002年 | 269篇 |
2001年 | 211篇 |
2000年 | 160篇 |
1999年 | 173篇 |
1998年 | 98篇 |
1997年 | 98篇 |
1996年 | 77篇 |
1995年 | 61篇 |
1994年 | 81篇 |
1993年 | 63篇 |
1992年 | 99篇 |
1991年 | 88篇 |
1990年 | 84篇 |
1989年 | 87篇 |
1988年 | 68篇 |
1987年 | 47篇 |
1986年 | 45篇 |
1985年 | 72篇 |
1984年 | 50篇 |
1983年 | 42篇 |
1982年 | 44篇 |
1981年 | 38篇 |
1980年 | 30篇 |
1979年 | 47篇 |
1978年 | 25篇 |
1977年 | 27篇 |
1976年 | 25篇 |
1974年 | 38篇 |
1973年 | 24篇 |
排序方式: 共有7614条查询结果,搜索用时 15 毫秒
991.
Regulation of alternative macrophage activation by galectin-3 总被引:3,自引:0,他引:3
MacKinnon AC Farnworth SL Hodkinson PS Henderson NC Atkinson KM Leffler H Nilsson UJ Haslett C Forbes SJ Sethi T 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(4):2650-2658
Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternative macrophage activation in bone marrow-derived macrophages in vitro and in resident lung and recruited peritoneal macrophages in vivo without affecting IFN-gamma/LPS-induced classical activation or IL-10-induced deactivation. IL-4-mediated alternative macrophage activation is inhibited by siRNA-targeted deletion of galectin-3 or its membrane receptor CD98 and by inhibition of PI3K. Increased galectin-3 expression and secretion is a feature of alternative macrophage activation. IL-4 stimulates galectin-3 expression and release in parallel with other phenotypic markers of alternative macrophage activation. By contrast, classical macrophage activation with LPS inhibits galectin-3 expression and release. Galectin-3 binds to CD98, and exogenous galectin-3 or cross-linking CD98 with the mAb 4F2 stimulates PI3K activation and alternative activation. IL-4-induced alternative activation is blocked by bis-(3-deoxy-3-(3-methoxybenzamido)-beta-D-galactopyranosyl) sulfane, a specific inhibitor of extracellular galectin-3 carbohydrate binding. These results demonstrate that a galectin-3 feedback loop drives alternative macrophage activation. Pharmacological modulation of galectin-3 function represents a novel therapeutic strategy in pathologies associated with alternatively activated macrophages. 相似文献
992.
993.
Neimanis AS Koopman HN Westgate AJ Nielsen K Leighton FA 《Journal of wildlife diseases》2008,44(2):480-485
Novel strains of Brucella recently have been discovered in marine mammals. To investigate Brucella exposure and infection in a general population of cetaceans, blood and tissue samples were collected and analyzed from wild harbor porpoises (Phocoena phocoena) incidentally caught in fishing gear in the Bay of Fundy, Canada. Two of 170 (1.2%) animals had detectable antibodies against Brucella, but no organisms were isolated from genital swabs or tissues from 22 and 8 porpoises, respectively. Genetic analysis of inflamed testes from 20 animals yielded no amplification of Brucella DNA. This is the first evidence of exposure to Brucella in porpoises from the western North Atlantic, and the prevalence is much lower than documented for conspecifics from the eastern North Atlantic. 相似文献
994.
995.
In vertebrates, the major histocompatibility complex (MHC) presents peptides to the immune system. In humans, MHCs are called
human leukocyte antigens (HLAs), and some of the loci encoding them are the most polymorphic in the human genome. Different
MHC molecules present different subsets of peptides, and knowledge of their binding specificities is important for understanding
the differences in the immune response between individuals. Knowledge of motifs may be used to identify epitopes, to understand
the MHC restriction of epitopes, and to compare the specificities of different MHC molecules. Algorithms that predict which
peptides MHC molecules bind have recently been developed and cover many different alleles, but the utility of these algorithms
is hampered by the lack of tools for browsing and comparing the specificity of these molecules. We have, therefore, developed
a web server, MHC motif viewer, that allows the display of the likely binding motif for all human class I proteins of the loci HLA A, B, C, and E and for
MHC class I molecules from chimpanzee (Pan troglodytes), rhesus monkey (Macaca mulatta), and mouse (Mus musculus). Furthermore, it covers all HLA-DR protein sequences. A special viewing feature, MHC fight, allows for display of the specificity of two different MHC molecules side by side. We show how the web server can be used
to discover and display surprising similarities as well as differences between MHC molecules within and between different
species. The MHC motif viewer is available at . 相似文献
996.
Peng Y Nielsen JE Cunningham JP McGraw EA 《Applied and environmental microbiology》2008,74(13):3943-3948
Wolbachia pipientis is an endosymbiotic bacterium present in diverse insect species. Although it is well studied for its dramatic effects on host reproductive biology, little is known about its effects on other aspects of host biology, despite its presence in a wide array of host tissues. This study examined the effects of three Wolbachia strains on two different Drosophila species, using a laboratory performance assay for insect locomotion in response to olfactory cues. The results demonstrate that Wolbachia infection can have significant effects on host responsiveness that vary with respect to the Wolbachia strain-host species combination. The wRi strain, native to Drosophila simulans, increases the basal activity level of the host insect as well as its responsiveness to food cues. In contrast, the wMel strain and the virulent wMelPop strain, native to Drosophila melanogaster, cause slight decreases in responsiveness to food cues but do not alter basal activity levels in the host. Surprisingly, the virulent wMelPop strain has very little impact on host responsiveness in D. simulans. This novel strain-host relationship was artificially created previously by transinfection. These findings have implications for understanding the evolution and spread of Wolbachia infections in wild populations and for Wolbachia-based vector-borne disease control strategies currently being developed. 相似文献
997.
Molecular modelling of the GIR1 branching ribozyme gives new insight into evolution of structurally related ribozymes
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Twin-ribozyme introns contain a branching ribozyme (GIR1) followed by a homing endonuclease (HE) encoding sequence embedded in a peripheral domain of a group I splicing ribozyme (GIR2). GIR1 catalyses the formation of a lariat with 3 nt in the loop, which caps the HE mRNA. GIR1 is structurally related to group I ribozymes raising the question about how two closely related ribozymes can carry out very different reactions. Modelling of GIR1 based on new biochemical and mutational data shows an extended substrate domain containing a GoU pair distinct from the nucleophilic residue that dock onto a catalytic core showing a different topology from that of group I ribozymes. The differences include a core J8/7 region that has been reduced and is complemented by residues from the pre-lariat fold. These findings provide the basis for an evolutionary mechanism that accounts for the change from group I splicing ribozyme to the branching GIR1 architecture. Such an evolutionary mechanism can be applied to other large RNAs such as the ribonuclease P. 相似文献
998.
999.
Lindsey Nielsen Dawn Meehan-Meola Annelisa Kilbourn Acacia Alcivar-Warren 《Conservation Genetics》2008,9(1):239-242
As the population sizes of the black and white rhinoceroses continues to decline, more efforts are needed in multiple areas
to help with the conservation efforts. One area being explored is the use of genetic diversity information to aid conservation
decisions. In this study, we designed 21 microsatellite primers for white and black rhinoceroses, 16 and 17 of which amplified
bands in the white and black rhinoceros, respectively. Out of these primers all 16 were polymorphic in the white rhinoceros
and 12 of the 17 were polymorphic in the black rhinoceros. The mean number of alleles was 3.31 and 2.12, the expected heterozygosities
were 0.420 and 0.372, and the observed heterozygosities were 0.436 and 0.322 for the white and black rhinoceroses, respectively.
Seven of the primers produced different allele sizes and variations that distinguished between black and white rhinoceroses.
Further genetic analyses with larger wild population sample sizes and markers are recommended to obtain a better understanding
of the genetic structure of the black and white rhinoceros populations in order to be useful in the conservation efforts of
these critically endangered species.
A. Kilbourn—In memoriam. 相似文献
1000.
Søren Bak Susanne Michelle Paquette Marc Morant Anne Vinther Morant Shigeki Saito Nanna Bjarnholt Mika Zagrobelny Kirsten Jørgensen Sarah Osmani Thomas Hamann Henrik Toft Simonsen Raquel Sanchez Pérez Torbjørn Bordier van Heeswijck Bodil Jørgensen Birger Lindberg Møller 《Phytochemistry Reviews》2008,7(1):209-209