全文获取类型
收费全文 | 603961篇 |
免费 | 65483篇 |
国内免费 | 366篇 |
出版年
2018年 | 6037篇 |
2017年 | 5879篇 |
2016年 | 8055篇 |
2015年 | 10048篇 |
2014年 | 11976篇 |
2013年 | 17435篇 |
2012年 | 19260篇 |
2011年 | 19658篇 |
2010年 | 13429篇 |
2009年 | 12273篇 |
2008年 | 17285篇 |
2007年 | 17786篇 |
2006年 | 16653篇 |
2005年 | 15964篇 |
2004年 | 15783篇 |
2003年 | 15068篇 |
2002年 | 14506篇 |
2001年 | 31184篇 |
2000年 | 30980篇 |
1999年 | 24077篇 |
1998年 | 7522篇 |
1997年 | 8082篇 |
1996年 | 7413篇 |
1995年 | 6841篇 |
1994年 | 6604篇 |
1993年 | 6607篇 |
1992年 | 18766篇 |
1991年 | 18056篇 |
1990年 | 17426篇 |
1989年 | 16825篇 |
1988年 | 15428篇 |
1987年 | 14416篇 |
1986年 | 13403篇 |
1985年 | 13151篇 |
1984年 | 10806篇 |
1983年 | 9059篇 |
1982年 | 6721篇 |
1981年 | 6090篇 |
1980年 | 5724篇 |
1979年 | 10057篇 |
1978年 | 7692篇 |
1977年 | 7070篇 |
1976年 | 6422篇 |
1975年 | 7193篇 |
1974年 | 7808篇 |
1973年 | 7658篇 |
1972年 | 6973篇 |
1971年 | 6294篇 |
1970年 | 5469篇 |
1969年 | 5214篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
941.
Joshua D. Doyle Jennifer E. Stencel-Baerenwald Courtney A. Copeland Jillian P. Rhoads Judy J. Brown Kelli L. Boyd James B. Atkinson Terence S. Dermody 《PLoS pathogens》2015,11(3)
Reovirus is a nonenveloped mammalian virus that provides a useful model system for studies of viral infections in the young. Following internalization into host cells, the outermost capsid of reovirus virions is removed by endosomal cathepsin proteases. Determinants of capsid disassembly kinetics reside in the viral σ3 protein. However, the contribution of capsid stability to reovirus-induced disease is unknown. In this study, we found that mice inoculated intramuscularly with a serotype 3 reovirus containing σ3-Y354H, a mutation that reduces viral capsid stability, succumbed at a higher rate than those infected with wild-type virus. At early times after inoculation, σ3-Y354H virus reached higher titers than wild-type virus at several sites within the host. Animals inoculated perorally with a serotype 1 reassortant reovirus containing σ3-Y354H developed exaggerated myocarditis accompanied by elaboration of pro-inflammatory cytokines. Surprisingly, unchallenged littermates of mice infected with σ3-Y354H virus displayed higher titers in the intestine, heart, and brain than littermates of mice inoculated with wild-type virus. Together, these findings suggest that diminished capsid stability enhances reovirus replication, dissemination, lethality, and host-to-host spread, establishing a new virulence determinant for nonenveloped viruses. 相似文献
942.
C A Kappel M C Dal Canto R W Melvold B S Kim 《Journal of immunology (Baltimore, Md. : 1950)》1991,147(12):4322-4326
Intracerebral inoculation of susceptible mice with Theiler's murine encephalomyelitis virus induces a demyelinating disease that is similar to human multiple sclerosis. This murine model for human multiple sclerosis is apparently immune-mediated and the genes involved in the immune response influence the outcome of disease susceptibility as observed with human multiple sclerosis. These genes include the MHC and TCR genes. However, the functional relationships among these genes on the disease susceptibility has not yet been studied. In this study, we demonstrate that the effect of the H-2s genotype from susceptible SJL/J mice overrides the resistant effect of the BALB/c TCR beta-chain gene in CXJ recombinant-inbred and BALB.S congenic mice. These results strongly suggest the presence of a hierarchy of genes involved in the immune response in Theiler's murine encephalomyelitis virus-induced demyelinating disease. 相似文献
943.
The RAD6 gene of Saccharomyces cerevisiae, which encodes a ubiquitin-conjugating enzyme, is required for DNA repair, DNA damage-induced mutagenesis and sporulation. To evaluate the biological relevance of the thioester adduct between RAD6 protein and ubiquitin, formed as an obligatory, transient intermediate during ubiquitin conjugation to substrates, we altered cysteine 88 in RAD6 to serine. Esterification with ubiquitin occurs at serine 88 in the mutant protein, but conjugation of ubiquitin to the test substrate histone H2A is inactivated. Phenotypically, strains harboring the rad6 Ser88 allele are indistinguishable from rad6 deletion (rad6 delta) mutant cells. These findings argue against ligation of ubiquitin at cysteine 88 acting as a functional switch of a cryptic biochemical activity in RAD6. 相似文献
944.
945.
Reuben S.E. Young Andrew P. Bowman Kaylyn D. Tousignant Berwyck L.J. Poad Jennifer H. Gunter Lisa K. Philp Colleen C. Nelson Shane R. Ellis Ron M.A. Heeren Martin C. Sadowski Stephen J. Blanksby 《Journal of lipid research》2022,63(6):100223
The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics. 相似文献
946.
947.
948.
949.
950.