全文获取类型
收费全文 | 1178篇 |
免费 | 67篇 |
专业分类
1245篇 |
出版年
2022年 | 14篇 |
2021年 | 13篇 |
2020年 | 12篇 |
2019年 | 10篇 |
2018年 | 15篇 |
2017年 | 15篇 |
2016年 | 24篇 |
2015年 | 63篇 |
2014年 | 47篇 |
2013年 | 82篇 |
2012年 | 82篇 |
2011年 | 70篇 |
2010年 | 54篇 |
2009年 | 34篇 |
2008年 | 71篇 |
2007年 | 82篇 |
2006年 | 61篇 |
2005年 | 76篇 |
2004年 | 61篇 |
2003年 | 61篇 |
2002年 | 61篇 |
2001年 | 20篇 |
2000年 | 17篇 |
1999年 | 20篇 |
1998年 | 15篇 |
1997年 | 10篇 |
1996年 | 11篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 7篇 |
1976年 | 3篇 |
1975年 | 6篇 |
1973年 | 6篇 |
1971年 | 6篇 |
排序方式: 共有1245条查询结果,搜索用时 15 毫秒
941.
942.
DNA Replication of Human Papillomavirus Type 31 Is Modulated by Elements of the Upstream Regulatory Region That Lie 5′ of the Minimal Origin 下载免费PDF全文
The viral replication factors E1 and E2 of papillomaviruses are necessary and sufficient to replicate plasmids containing the minimal origin of DNA replication in transient assays. Under physiological conditions, the upstream regulatory region (URR) governs expression of the early viral genes. To determine the effect of URR elements on E1 and E2 expression specifically, and on the regulation of DNA replication during the various phases of the viral life cycle, we carried out a systematic replication study with entire genomes of human papillomavirus type 31 (HPV31), a high-risk oncogenic type. We constructed a series of URR deletions, spacer replacements, and point mutations to analyze the role of the keratinocyte enhancer (KE) element, the auxiliary enhancer (AE) domain, and the L1-proximal end of the URR (5′-URR domain) in DNA replication during establishment, maintenance, and vegetative viral DNA amplification. Using transient and stable replication assays, we demonstrate that the KE and AE are necessary for efficient E1 and E2 gene expression and that the KE can also directly modulate viral replication. KE-mediated activation of replication is dependent on the position and orientation of the element. Mutation of either one of the four Ap1 sites, the single Sp1 site, or the binding site for the uncharacterized footprint factor 1 reduced replication efficiency through decreased expression of E1 and E2. Furthermore, the 5′-URR domain and the Oct1 DNA binding site are dispensable for viral replication, since such HPV31 mutants are able to replicate efficiently in a transient assay, maintain a stable copy number over several cell generations, and amplify viral DNA under vegetative conditions. Interestingly, deletion of the 5′-URR domain leads to increased transient and stable replication levels. These findings suggest that elements in the HPV31 URR outside the minimal origin modulate viral replication through both direct and indirect mechanisms. 相似文献
943.
STAT3 activation abrogates growth factor dependence and contributes to head and neck squamous cell carcinoma tumor growth in vivo. 总被引:14,自引:0,他引:14
944.
Michiya Matsusaki Takeshi Serizawa Akio Kishida Takeshi Endo Mitsuru Akashi 《Bioconjugate chemistry》2002,13(1):23-28
gamma-Poly(glutamic acid) (gamma-PGA), which is produced by Bacillus subtilis, was sulfonated using 2-aminoethane-1-sulfonic acid (taurine) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC) to give sulfonated gamma-PGA (gamma-PGA-sulfonate). From (1)H NMR spectroscopy and IR spectroscopy, it was confirmed that taurine was introduced to the side chain of gamma-PGA via an amide linkage. By altering the synthetic conditions, it was possible to control the content of sulfonate in gamma-PGA-sulfonate. Anticoagulant activity was investigated in order to evaluate the biological activity of gamma-PGA-sulfonate by the Lee-White test. The clotting time was prolonged when the concentration of gamma-PGA-sulfonate on the degree of sulfonation was increased. It becomes clear that gamma-PGA-sulfonate is potentially useful for various medical applications, such as drug delivery, tissue engineering, and medical materials. 相似文献
945.
Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation. 总被引:4,自引:0,他引:4
Hitoshi Nishizawa Kazuya Yamagata Iichiro Shimomura Masahiko Takahashi Hiroshi Kuriyama Ken Kishida Kikuko Hotta Hiroyuki Nagaretani Norikazu Maeda Morihiro Matsuda Shinji Kihara Tadashi Nakamura Hidekazu Nishigori Hideaki Tomura David D Moore Jun Takeda Tohru Funahashi Yuji Matsuzawa 《The Journal of biological chemistry》2002,277(2):1586-1592
946.
947.
Yasui A Nishizawa H Okuno Y Morita K Kobayashi H Kawai K Matsuda M Kishida K Kihara S Kamei Y Ogawa Y Funahashi T Shimomura I 《Biochemical and biophysical research communications》2007,364(2):358-365
Musclin is a novel skeletal muscle-derived secretory factor, whose mRNA level is markedly regulated by nutritional status. In the present study, we investigated the mechanism of musclin mRNA regulation by insulin. In C2C12 myocytes, insulin-induced upregulation of musclin mRNA was significantly decreased by treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, and was abolished in C2C12 myocytes stably expressing a constitutively active Foxo1 (Foxo1-3A), suggesting the involvement of Foxo1 in the regulation of musclin mRNA. Promoter deletion analysis of musclin promoter revealed that the region of −303/−123 is important for the repression of promoter activity by Foxo1. Chromatin immunoprecipitation assay showed that Foxo1 bound to musclin promoter. Musclin mRNA level was markedly downregulated in gastrocnemius muscle of Foxo1 transgenic mice. Our results demonstrated that Foxo1 downregulates musclin mRNA expression both in vitro and in vivo, which should explain insulin-mediated upregulation of this gene in muscle cells. 相似文献
948.
949.
Kinesin is a linear motor protein driven by energy released by ATP hydrolysis. In the present work, we genetically installed an M13 peptide sequence into Loop 12 of kinesin, which is one of the major microtubule binding regions of the protein. Because the M13 sequence has high affinity for Ca(2+)-calmodulin, the association of the engineered kinesin with microtubules showed a steep Ca(2+)-dependency in ATPase activity at Ca(2+) concentrations of pCa 6.5-8. The calmodulin-binding domain of plant kinesin-like calmodulin-binding protein is also known to confer Ca(2+)-calmodulin regulation to kinesins. Unlike this plant kinesin, however, our novel engineered kinesin achieves this regulation while maintaining the interaction between kinesin and microtubules. The engineered kinesin is switched on/off reversibly by an external signal (i.e., Ca(2+)-calmodulin) and, thus, can be used as a model system for a bio/nano-actuator. 相似文献
950.
Hiroyuki Satoh Naomi Inokuchi Yasuhiro Nagae Taro Okazaki 《Journal of molecular evolution》1999,49(1):122-129
The β-globin gene cluster of Wistar rat was extensively cloned and the embryonic genes were mapped and sequenced. Four overlapping
λ Dash recombinant clones cover about 31 kb and contain four nonadult β-globin genes, 5′–ε1–γ1–γ2–ψγ3–3′. The ε1 and γ2 are
active genes, since their protein products were detected in the fetal stage of the rat (Iwahara et al., J Biochem 119:360–366,
1996). The γ1 locus might be a pseudogene, since the ATA box in the promoter region is mutated to GTA; however, no other defect
is observed. The ψγ3 locus is a truncated pseudogene because a 19-base deletion, which causes a shift of the reading frame,
is observed between the second nucleotide of the putative codon 68 and codon 76. A sequence comparison suggests that the ψγ3
might be produced by a gene conversion event of the proto-γ-globin gene set. Possible histories of the evolution of rat nonadult
β-globin genes are discussed.
Received: 6 August 1998 / Accepted: 12 February 1999 相似文献