全文获取类型
收费全文 | 6648篇 |
免费 | 649篇 |
国内免费 | 3篇 |
专业分类
7300篇 |
出版年
2024年 | 9篇 |
2023年 | 77篇 |
2022年 | 145篇 |
2021年 | 276篇 |
2020年 | 155篇 |
2019年 | 226篇 |
2018年 | 181篇 |
2017年 | 190篇 |
2016年 | 296篇 |
2015年 | 510篇 |
2014年 | 555篇 |
2013年 | 566篇 |
2012年 | 727篇 |
2011年 | 664篇 |
2010年 | 371篇 |
2009年 | 325篇 |
2008年 | 411篇 |
2007年 | 368篇 |
2006年 | 309篇 |
2005年 | 278篇 |
2004年 | 236篇 |
2003年 | 155篇 |
2002年 | 139篇 |
2001年 | 27篇 |
2000年 | 10篇 |
1999年 | 17篇 |
1998年 | 10篇 |
1997年 | 13篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有7300条查询结果,搜索用时 0 毫秒
21.
22.
23.
Alexander M. Milner Jessica L. Picken Megan J. Klaar Anne L. Robertson Leonie R. Clitherow Lawrence Eagle Lee E. Brown 《Ecology and evolution》2018,8(16):8354-8363
Floods have a major influence in structuring river ecosystems. Considering projected increases in high‐magnitude rainfall events with climate change, major flooding events are expected to increase in many regions of the world. However, there is uncertainty about the effect of different flooding regimes and the importance of flood timing in structuring riverine habitats and their associated biotic communities. In addition, our understanding of community response is hindered by a lack of long‐term datasets to evaluate river ecosystem resilience to flooding. Here we show that in a river ecosystem studied for 30 years, a major winter flood reset the invertebrate community to a community similar to one that existed 15 years earlier. The community had not recovered to the preflood state when recurrent summer flooding 9 years later reset the ecosystem back to an even earlier community. Total macroinvertebrate density was reduced in the winter flood by an order of magnitude more than the summer flood. Meiofaunal invertebrates were more resilient to the flooding than macroinvertebrates, possibly due to their smaller body size facilitating greater access to in‐stream refugia. Pacific pink salmon escapement was markedly affected by the winter flood when eggs were developing in redds, compared to summer flooding, which occurred before the majority of eggs were laid. Our findings inform a proposed conceptual model of three possible responses to flooding by the invertebrate community in terms of switching to different states and effects on resilience to future flooding events. In a changing climate, understanding these responses is important for river managers to mitigate the biological impacts of extreme flooding effects. 相似文献
24.
The COMPASS family of H3K4 methylases in Drosophila 总被引:1,自引:0,他引:1
Mohan M Herz HM Smith ER Zhang Y Jackson J Washburn MP Florens L Eissenberg JC Shilatifard A 《Molecular and cellular biology》2011,31(21):4310-4318
Methylation of histone H3 lysine 4 (H3K4) in Saccharomyces cerevisiae is implemented by Set1/COMPASS, which was originally purified based on the similarity of yeast Set1 to human MLL1 and Drosophila melanogaster Trithorax (Trx). While humans have six COMPASS family members, Drosophila possesses a representative of the three subclasses within COMPASS-like complexes: dSet1 (human SET1A/SET1B), Trx (human MLL1/2), and Trr (human MLL3/4). Here, we report the biochemical purification and molecular characterization of the Drosophila COMPASS family. We observed a one-to-one similarity in subunit composition with their mammalian counterparts, with the exception of LPT (lost plant homeodomains [PHDs] of Trr), which copurifies with the Trr complex. LPT is a previously uncharacterized protein that is homologous to the multiple PHD fingers found in the N-terminal regions of mammalian MLL3/4 but not Drosophila Trr, indicating that Trr and LPT constitute a split gene of an MLL3/4 ancestor. Our study demonstrates that all three complexes in Drosophila are H3K4 methyltransferases; however, dSet1/COMPASS is the major monoubiquitination-dependent H3K4 di- and trimethylase in Drosophila. Taken together, this study provides a springboard for the functional dissection of the COMPASS family members and their role in the regulation of histone H3K4 methylation throughout development in Drosophila. 相似文献
25.
Bharath Balu Chitra Chauhan Steven P Maher Douglas A Shoue Jessica C Kissinger Malcolm J Fraser John H Adams 《BMC microbiology》2009,9(1):83
Background
Much of thePlasmodium falciparumgenome encodes hypothetical proteins with limited homology to other organisms. A lack of robust tools for genetic manipulation of the parasite limits functional analysis of these hypothetical proteins and other aspects of thePlasmodiumgenome. Transposon mutagenesis has been used widely to identify gene functions in many organisms and would be extremely valuable for functional analysis of thePlasmodiumgenome. 相似文献26.
Pei Y Hancock PJ Zhang H Bartz R Cherrin C Innocent N Pomerantz CJ Seitzer J Koser ML Abrams MT Xu Y Kuklin NA Burke PA Sachs AB Sepp-Lorenzino L Barnett SF 《RNA (New York, N.Y.)》2010,16(12):2553-2563
Effective small interfering RNA (siRNA)-mediated therapeutics require the siRNA to be delivered into the cellular RNA-induced silencing complex (RISC). Quantitative information of this essential delivery step is currently inferred from the efficacy of gene silencing and siRNA uptake in the tissue. Here we report an approach to directly quantify siRNA in the RISC in rodents and monkey. This is achieved by specific immunoprecipitation of the RISC from tissue lysates and quantification of small RNAs in the immunoprecipitates by stem-loop PCR. The method, expected to be independent of delivery vehicle and target, is label-free, and the throughput is acceptable for preclinical animal studies. We characterized a lipid-formulated siRNA by integrating these approaches and obtained a quantitative perspective on siRNA tissue accumulation, RISC loading, and gene silencing. The described methodologies have utility for the study of silencing mechanism, the development of siRNA therapeutics, and clinical trial design. 相似文献
27.
28.
Elf5 is essential for early embryogenesis and mammary gland development during pregnancy and lactation 下载免费PDF全文
Zhou J Chehab R Tkalcevic J Naylor MJ Harris J Wilson TJ Tsao S Tellis I Zavarsek S Xu D Lapinskas EJ Visvader J Lindeman GJ Thomas R Ormandy CJ Hertzog PJ Kola I Pritchard MA 《The EMBO journal》2005,24(3):635-644
Elf5 is an epithelial-specific ETS factor. Embryos with a null mutation in the Elf5 gene died before embryonic day 7.5, indicating that Elf5 is essential during mouse embryogenesis. Elf5 is also required for proliferation and differentiation of mouse mammary alveolar epithelial cells during pregnancy and lactation. The loss of one functional allele led to complete developmental arrest of the mammary gland in pregnant Elf5 heterozygous mice. A quantitative mRNA expression study and Western blot analysis revealed that decreased expression of Elf5 correlated with the downregulation of milk proteins in Elf5(+/-) mammary glands. Mammary gland transplants into Rag(-/-) mice demonstrated that Elf5(+/-) mammary alveolar buds failed to develop in an Elf5(+/+) mammary fat pad during pregnancy, demonstrating an epithelial cell autonomous defect. Elf5 expression was reduced in Prolactin receptor (Prlr) heterozygous mammary glands, which phenocopy Elf5(+/-) glands, suggesting that Elf5 and Prlr are in the same pathway. Our data demonstrate that Elf5 is essential for developmental processes in the embryo and in the mammary gland during pregnancy. 相似文献
29.
30.
Justin Mancini Brooke Weckselblatt Yoonjie K. Chung Julia C. Durante Steven Andelman Jessica Glaubman Justin D. Dorff Samhita Bhargava Rebeccah S. Lijek Katherine P. Unger Iruka N. Okeke 《Journal of bacteriology》2011,193(18):4813-4820
Heat-resistant agglutinin 1 (Hra1) is an accessory colonization factor of enteroaggregative Escherichia coli (EAEC) strain 042. Tia, a close homolog of Hra1, is an invasin and adhesin that has been described in enterotoxigenic E. coli. We devised a PCR-restriction fragment length polymorphism screen for the associated genes and found that they occur among 55 (36.7%) of the enteroaggregative E. coli isolates screened, as well as lower proportions of enterotoxigenic, enteropathogenic, enterohemorrhagic, and commensal E. coli isolates. Overall, 25%, 8%, and 3% of 150 EAEC strains harbored hra1 alone, tia alone, or both genes, respectively. One EAEC isolate, 60A, produced an amplicon with a unique restriction profile, distinct from those of hra1 and tia. We cloned and sequenced the full-length agglutinin gene from strain 60A and have designated it hra2. The hra2 gene was not detected in any of 257 diarrheagenic E. coli isolates in our collection but is present in the genome of Salmonella enterica serovar Heidelberg strain SL476. The cloned hra2 gene from strain 60A, which encodes a predicted amino acid sequence that is 64% identical to that of Hra1 and 68% identical to that of Tia, was sufficient to confer adherence on E. coli K-12. We constructed an hra2 deletion mutant of EAEC strain 60A. The mutant was deficient in adherence but not autoaggregation or invasion, pointing to a functional distinction from the autoagglutinin Hra1 and the Tia invasin. Hra1, Tia, and the novel accessory adhesin Hra2 are members of a family of integral outer membrane proteins that confer different colonization-associated phenotypes. 相似文献