全文获取类型
收费全文 | 43348篇 |
免费 | 3684篇 |
国内免费 | 3110篇 |
出版年
2023年 | 466篇 |
2022年 | 583篇 |
2021年 | 1821篇 |
2020年 | 1453篇 |
2019年 | 1839篇 |
2018年 | 1789篇 |
2017年 | 1297篇 |
2016年 | 1890篇 |
2015年 | 2888篇 |
2014年 | 3314篇 |
2013年 | 3450篇 |
2012年 | 4114篇 |
2011年 | 3699篇 |
2010年 | 2333篇 |
2009年 | 2015篇 |
2008年 | 2481篇 |
2007年 | 2258篇 |
2006年 | 1925篇 |
2005年 | 1646篇 |
2004年 | 1371篇 |
2003年 | 1215篇 |
2002年 | 1039篇 |
2001年 | 703篇 |
2000年 | 569篇 |
1999年 | 597篇 |
1998年 | 378篇 |
1997年 | 354篇 |
1996年 | 307篇 |
1995年 | 266篇 |
1994年 | 269篇 |
1993年 | 181篇 |
1992年 | 261篇 |
1991年 | 214篇 |
1990年 | 165篇 |
1989年 | 128篇 |
1988年 | 97篇 |
1987年 | 120篇 |
1986年 | 97篇 |
1985年 | 80篇 |
1984年 | 63篇 |
1983年 | 43篇 |
1982年 | 42篇 |
1981年 | 29篇 |
1980年 | 26篇 |
1979年 | 29篇 |
1978年 | 21篇 |
1977年 | 19篇 |
1975年 | 26篇 |
1974年 | 21篇 |
1972年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.
Splenic gene expression profiling in White Leghorn layer inoculated with the Salmonella enterica serovar Enteritidis 下载免费PDF全文
Salmonella enterica serovar Enteritidis (SE) is a foodborne pathogen that can threaten human health through contaminated poultry products. Live poultry, chicken eggs and meat are primary sources of human salmonellosis. To understand the genetic resistance of egg‐type chickens in response to SE inoculation, global gene expression in the spleen of 20‐week‐old White Leghorn was measured using the Agilent 4 × 44 K chicken microarray at 7 and 14 days following SE inoculation (dpi). Results showed that there were 1363 genes significantly differentially expressed between inoculated and non‐inoculated groups at 7 dpi (I7/N7), of which 682 were up‐regulated and 681 were down‐regulated genes. By contrast, 688 differentially expressed genes were observed at 14 dpi (I14/N14), of which 371 were up‐regulated genes and 317 were down‐regulated genes. There were 33 and 28 immune‐related genes significantly differentially expressed in the comparisons of I7/N7 and I14/N14 respectively. Functional annotation revealed that several Gene Ontology (GO) terms related to immunity were significantly enriched between the inoculated and non‐inoculated groups at 14 dpi but not at 7 dpi, despite a similar number of immune‐related genes identified between I7/N7 and I14/N14. The immune response to SE inoculation changes with different time points following SE inoculation. The complicated interaction between the immune system and metabolism contributes to the immune responses to SE inoculation of egg‐type chickens at 14 dpi at the onset of lay. GC, TNFSF8, CD86, CD274, BLB1 and BLB2 play important roles in response to SE inoculation. The results from this study will deepen the current understanding of the genetic response of the egg‐type chicken to SE inoculation at the onset of egg laying. 相似文献
3.
4.
Three saponins from Oxytropis species. 总被引:2,自引:0,他引:2
Three flavonoids and three saponins have been isolated from Oxytropis species. Their structures were determined as isorhamnetin-3-O-beta-D-glucoside, rhamnetin-3-O-beta-D-galactoside, apigenin, 3-O-[alpha-L-rhamnopyranosyl (1----2)-beta-D-glucopyranosyl(1----4)-beta-D-glucuronopyranosyl]+ ++soyasapogenol B, 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucuronopyranosyl] azukisapogenol and a new saponin 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucopyranosyl]-25-O-alpha-L- rhamnopyranosyl-(20S,24S)-3 beta,16 beta, 20,24,25-pentahydroxy-9,19-cycloanostane. 相似文献
5.
W. D. Roof H. Q. Fang K. D. Young Jianling Sun & Ry Young 《Molecular microbiology》1997,25(6):1031-1046
slyD encodes a 196 amino acid polypeptide that is a member of the FKBP family of cis–trans peptidyl–prolyl isomerases (PPIases). slyD mutations affect plaque formation by the phage φX174 by blocking the action of the phage lysis protein E. Here we describe the selection of a set of spontaneous slyD mutations conferring resistance to the expression of gene E from a plasmid. These mutations occur disproportionately in residues of SlyD that, based on the structure of the prototype mammalian FKBP12, make ligand contacts with immunosuppressing drug molecules or are conserved in other FKBP proteins. A wide variation in the plating efficiency of φX174 on these E R strains is observed, relative to the parental, indicating that these alleles differ widely in residual SlyD activity. Moreover, it is found that slyD mutations cause significant growth rate defects in Escherichia coli B and C backgrounds. Finally, overexpression of slyD causes filamentation of the host. Thus, among the FKBP genes found in organisms across the evolutionary spectrum, slyD is unique in having three distinct drug-independent phenotypes. 相似文献
6.
Unconventional Sequence Requirement for Viral Late Gene Core Promoters of Murine Gammaherpesvirus 68
Elaine Wong-Ho Ting-Ting Wu Zoe H. Davis Bingqing Zhang Jian Huang Hao Gong Hongyu Deng Fenyong Liu Britt Glaunsinger Ren Sun 《Journal of virology》2014,88(6):3411-3422
Infection with the human gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi''s sarcoma-associated herpesvirus (KSHV), is associated with several cancers. During lytic replication of herpesviruses, viral genes are expressed in an ordered cascade. However, the mechanism by which late gene expression is regulated has not been well characterized in gammaherpesviruses. In this study, we have investigated the cis element that mediates late gene expression during de novo lytic infection with murine gammaherpesvirus 68 (MHV-68). A reporter system was established and used to assess the activity of viral late gene promoters upon infection with MHV-68. It was found that the viral origin of lytic replication, orilyt, must be on the reporter plasmid to support activation of the late gene promoter. Furthermore, the DNA sequence required for the activation of late gene promoters was mapped to a core element containing a distinct TATT box and its neighboring sequences. The critical nucleotides of the TATT box region were determined by systematic mutagenesis in the reporter system, and the significance of these nucleotides was confirmed in the context of the viral genome. In addition, EBV and KSHV late gene core promoters could be activated by MHV-68 lytic replication, indicating that the mechanisms controlling late gene expression are conserved among gammaherpesviruses. Therefore, our results on MHV-68 establish a solid foundation for mechanistic studies of late gene regulation. 相似文献
7.
Pasupathi Sundaramoorthy Jae Jun Sim Yeong-Su Jang Siddhartha Kumar Mishra Keun-Yeong Jeong Poonam Mander Oh Byung Chul Won-Sik Shim Seung Hyun Oh Ky-Youb Nam Hwan Mook Kim 《PloS one》2015,10(1)
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer. 相似文献
8.
Eun Jin Park Joon Young Song Min Ju Choi Ji Ho Jeon Jah-yeon Choi Tae Un Yang Kyung Wook Hong Ji Yun Noh Hee Jin Cheong Woo Joo Kim 《The Korean journal of parasitology》2014,52(4):425-428
A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia. 相似文献
9.
10.