全文获取类型
收费全文 | 2139篇 |
免费 | 33篇 |
国内免费 | 28篇 |
专业分类
2200篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 22篇 |
2021年 | 41篇 |
2020年 | 24篇 |
2019年 | 46篇 |
2018年 | 57篇 |
2017年 | 28篇 |
2016年 | 32篇 |
2015年 | 99篇 |
2014年 | 246篇 |
2013年 | 220篇 |
2012年 | 221篇 |
2011年 | 299篇 |
2010年 | 204篇 |
2009年 | 71篇 |
2008年 | 94篇 |
2007年 | 81篇 |
2006年 | 61篇 |
2005年 | 62篇 |
2004年 | 40篇 |
2003年 | 30篇 |
2002年 | 28篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 10篇 |
1997年 | 4篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 7篇 |
1984年 | 16篇 |
1983年 | 27篇 |
1982年 | 14篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 1篇 |
排序方式: 共有2200条查询结果,搜索用时 0 毫秒
1.
Controlled generation of reactive oxygen species orchestrates numerous physiological signaling events (Finkel, T. (2011) Signal transduction by reactive oxygen species. J. Cell Biol. 194, 7–15). A major cellular target of reactive oxygen species is the thiol side chain (RSH) of Cys, which may assume a wide range of oxidation states (i.e. −2 to +4). Within this context, Cys sulfenic (Cys-SOH) and sulfinic (Cys-SO2H) acids have emerged as important mechanisms for regulation of protein function. Although this area has been under investigation for over a decade, the scope and biological role of sulfenic/sulfinic acid modifications have been recently expanded with the introduction of new tools for monitoring cysteine oxidation in vitro and directly in cells. This minireview discusses selected recent examples of protein sulfenylation and sulfinylation from the literature, highlighting the role of these post-translational modifications in cell signaling. 相似文献
2.
Small ubiquitin-like modifier (SUMO), a member of the ubiquitin-related protein family, is covalently conjugated to lysine residues of its substrates in a process referred to as SUMOylation. SUMOylation occurs through a series of enzymatic reactions analogous to that of the ubiquitination pathway, resulting in modification of the biochemical and functional properties of substrates. To date, four mammalian SUMO isoforms, a single heterodimeric SUMO-activating E1 enzyme SAE1/SAE2, a single SUMO-conjugating E2 enzyme ubiquitin-conjugating enzyme E2I (UBC9), and a few subgroups of SUMO E3 ligases have been identified. Several SUMO E3 ligases such as topoisomerase I binding, arginine/serine-rich (TOPORS), TNF receptor-associated factor 7 (TRAF7), and tripartite motif containing 27 (TRIM27) have dual functions as ubiquitin E3 ligases. Here, we demonstrate that the ubiquitin E3 ligase UHRF2 also acts as a SUMO E3 ligase. UHRF2 effectively enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. In addition, the SUMO E3 activity of UHRF2 on ZNF131 depends on the presence of SET and RING finger-associated and nuclear localization signal-containing region domains, whereas the critical ubiquitin E3 activity RING domain is dispensable. Our findings suggest that UHRF2 has independent functional domains and regulatory mechanisms for these two distinct enzymatic activities. 相似文献
3.
Summary According to Nagl and Fusenig (1979) the structure and ultrastructure of plant nuclei is species-specific and is determined by the DNA (2C) value and the amount of the repetitive DNA. Light and electron microscopic observations ofZea mays L.,Pisum sativum L., andPhaseolus vulgaris L. nuclei led us to define their organization as chromonematic, chronomeric and chromocentric, respectively. Nuclear proteins, soluble in 0.4N H2SO4 and 0.74M HC1O4, were extracted from isolated nuclei and resolved according to their solubility and mobility in SDS and acetic acid-urea PAGE and 2D-Triton X 100 PAGE. Differences in the variants (and modifications) of the H 1 histone class and the nucleosomal H 2 A, H 2 B, and H 3 isoforms probably reflect that species-specific nuclear ultrastructure is based, not only on the heterogeneity and the quantity of DNA, but also on the diversity of the protein component of chromatin.Abbreviations MES
Morpholinoethane sulfonic acid
- PMSF
phenylmethylsulphonyl fluoride
- DMSO
dimethylsulfoxid
- SDS
sodium dodecylsulfate
- TEMED N, N, N
N-tetramethylethylen-diamin
- PAGE
polyacrylamide gel electrophoresis 相似文献
4.
5.
Ichiro Oohara Akira Suyama Akiyoshi Wada 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,741(3)
Poly(l-glutamic acid) has been reported to mediate in vitro nucleosome assembly (Stein, A., Whitlock, J.P., Jr. and Bina, M. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 5000–5004). To study the reaction mechanism, we have reconstituted nucleosome core particles from chicken erythrocyte core DNA and core histones in the presence of poly(l-glutamic acid) and analyzed the assembly products by polyacrylamide gel electrophoresis. Poly(l-glutamic acid), which binds and forms a large complex with core histones, is replaced with core DNA in the reconstitution process. When histone-poly(l-glutamic acid) complex and core DNA are mixed with a histone:DNA ratio of 1.0, the yield of core particles increases by prolonged reconstitution time. Two phases with a distinct time range appear in the process. In the fast phase within 30 min, 60% of the DNA is involved in products containing histones: reconstituted core particles, a larger nucleoprotein complex and aggregation. In the second phase, the remaining DNA and the DNA in the aggregation decrease, and the core particles increase slowly. The yield of core particles is approx. 60% after 24 h. The slow phase is not observed by reconstitution with a histone:DNA ratio of 2.0 in the initial mixture. The reaction scheme of the assembly process derived from these data is given. Based on the in vitro reaction scheme, the possible role of in vivo ‘nucleosome assembly factors’ is also discussed. 相似文献
6.
Y.M. Bhatnagar R.D. Faulkner 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,739(1):132-136
Electrophoretic analysis of the nucleosomal histones from MN1 and MN2 subpopulations of the seminiferous tubules in gels containing either 6.25 or 2.5 M urea revealed the presence of testis specific histone H2S, H1 and protein ‘A’ in addition to the somatic histones in the core protein complex. Size analysis indicated the presence of a 150–160 bp DNA segment in the MNI subpopulation, whereas, an approx 180 bp DNA fragment was present in the MN2 subpopulation of both liver and tubule nucleosomes. These data suggest an extensive remodeling of the nucleosomal core protein complex during mammalian spermatogenesis. 相似文献
7.
Peter E. Prevelige Gerald D. Fasman 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,739(1):85-96
Core histones, (H2A,H2B,H3,H4)2, were reconstituted with the synthethic polynucleotides poly(dA-dT)·poly(dA-dT) and poly(dG-dC)·poly(dG-dC) to yield synthetic chromatins containing 200 basepairs per octamer. These synthetic chromatins displayed a 36% decrease in the circular dichroism (CD) peak ellipticity from the value of the polynucleotide free in solution; the poly(dA-dT)·poly(dA-dT)/chromatin showed an increase in the complexity of the thermal denaturation profile compared to that of the polynucleotide. Both the temperature of maximum for each transition (Tm) and the relative amount of poly(dA-dT)·poly(dA-dT) in the synthetic chromatin melting in each of the four thermal transitions is a function of the ionic strength over the 0–5 mM sodium phosphate range (0.25 mM EDTA, pH 7.0); a shift of material toward higher melting transitions was observed with increasing ionic strength. The CD peak ellipticity value for both synthetic chromatins was ionic strength-independent over the 0–5 mM sodium phosphate range. These results are in contrast to those observed with stripped chicken erythrocyte chromatin (Fulmer, A. and Fasman, G.D. (1979) Biopolymers 18, 2875–2891), where an ionic strength dependence was found. Differences in the CD spectra between poly(dA-dT)·poly(dA-dT)/chromatin, poly(dG-dC)·poly(dG-dC)/chromatin and stripped chicken erythrocyte chromatin suggest subtle differences in assembly. Finally, the temperature dependence of the CD spectra of poly(dA-dT)·poly(dA-dT)-containing synthetic chromatin, which is similar to that for the polynucleotide, suggests the core histone bound polynucleotide has a large degree of conformational flexibility allowing it to undergo the premelt transition. 相似文献
8.
Summary The organization of histone gene clusters of the duckCairina moschata was studied in the DNA inserts of two recombinant phage that overlap and feature identical histone gene arrangements but differ in sequence details and in the extent of repetition of an AT-rich motif in one of the nontranscribed spacer regions. These few but substantial differences between otherwise nearly identical histone gene groups suggest that we have independently isolated alleles of the same site of the duck genome or that this gene arrangement occurs (with slight variations) more than once per haploid genome. Within the histone gene cluster described, H3 and H4 genes are duplicated (with inverted orientation), whereas one H1 gene is flanked by single H2A and H2B genes. The arrangement of duck histone genes described here is identical to a subsection of the chicken genome but differs from any other published histone gene cluster. 相似文献
9.
10.
Susumu Ikegami Yasunori Ooe Takahiko Shimizu Toshihiko Kasahara Tatsuhiko Tsuruta Masako Kijima Minoru Yoshida Teruhiko Beppu 《Development genes and evolution》1993,202(3):144-151
Summary External application of 10 rig/ml (R)-trichostatin A (TSA), a potent and specific inhibitor of mammalian histone deacetylase, to the embryo of the starfish Asterina pectinifera inhibited development during the early gastrula stage before formation of mesenchyme cells. The TSA-sensitive period was limited to the mid-blastula stage before hatching. The pulse-chase experiment clearly demonstrated that TSA induced an accumulation of acetylated histone species in blastulae through inhibition of historic deacetylation. Similar blockage of development at the early gastrula stage was observed with n-butyrate, which has been known as a weak inhibitor of historic deacetylase. These results suggest an intimate role for historic acetylation-deacetylation equilibria in starfish development.
Correspondence to: S. Ikegami 相似文献