全文获取类型
收费全文 | 4505篇 |
免费 | 524篇 |
国内免费 | 1篇 |
出版年
2021年 | 53篇 |
2020年 | 39篇 |
2019年 | 37篇 |
2018年 | 63篇 |
2017年 | 50篇 |
2016年 | 106篇 |
2015年 | 162篇 |
2014年 | 152篇 |
2013年 | 191篇 |
2012年 | 242篇 |
2011年 | 256篇 |
2010年 | 159篇 |
2009年 | 145篇 |
2008年 | 217篇 |
2007年 | 240篇 |
2006年 | 219篇 |
2005年 | 216篇 |
2004年 | 219篇 |
2003年 | 194篇 |
2002年 | 201篇 |
2001年 | 75篇 |
2000年 | 71篇 |
1999年 | 79篇 |
1998年 | 71篇 |
1997年 | 65篇 |
1996年 | 71篇 |
1995年 | 54篇 |
1994年 | 49篇 |
1993年 | 58篇 |
1992年 | 64篇 |
1991年 | 101篇 |
1990年 | 67篇 |
1989年 | 58篇 |
1988年 | 44篇 |
1987年 | 58篇 |
1986年 | 37篇 |
1985年 | 63篇 |
1984年 | 58篇 |
1983年 | 49篇 |
1982年 | 42篇 |
1981年 | 44篇 |
1980年 | 51篇 |
1979年 | 34篇 |
1978年 | 27篇 |
1977年 | 44篇 |
1976年 | 47篇 |
1975年 | 36篇 |
1974年 | 36篇 |
1973年 | 26篇 |
1968年 | 25篇 |
排序方式: 共有5030条查询结果,搜索用时 15 毫秒
971.
Marko Z. Radic Michael Saghbini Terry S. Elton Raymond Reeves Barbara A. Hamkalo 《Chromosoma》1992,101(10):602-608
The experiments described were designed to test the hypothesis that the (A+T)-specific DNA binding ligands Hoechst 33258 and distamycin A affect the condensation of mouse centromeric heterochromatin by competing for binding to satellite DNA with one or more chromosomal proteins. The studies focused on the nonhistone chromosomal protein HMG-I since its binding properties predict it would be a target for competition. Gel mobility shift assays show that HMG-I forms specific complexes with satellite DNA and that the formation of these complexes is competed for by both Hoechst and distamycin. In addition, methidium propyl EDTA Fe(II) [MPE Fe(II)] footprints of ligand-satellite DNA complexes showed essentially the same protection pattern for both drugs and a similar, but not identical, HMG-I footprint. If these in vitro results reflect the in vivo situation then the incomplete condensation of centromeric heterochromatin observed when mouse cells are grown in the presence of either chemical ligand could be a consequence of competition for binding of HMG-I (and possibly other proteins) to satellite DNA.by E.R. Schmidt 相似文献
972.
973.
Pascual Juan M.; Shieh Char-Chang; Kirsch Glenn E.; Brown Arthur M. 《American journal of physiology. Cell physiology》1997,273(6):C1849
Opening and closing of voltage-operated channels requires theinteraction of diverse structural elements. One approach to theidentification of channel domains that participate in gating is tolocate the sites of action of modifiers. Covalent reaction of Kv2.1channels with the neutral, sulfhydryl-specificmethylmethanethiosulfonate (MMTS) caused a slowing of channel gatingwith a predominant effect on the kinetics of activation. These effectswere also obtained after intracellular, but not extracellular,application of a charged MMTS analog. Single channel analysis revealedthat MMTS acted primarily by prolonging the latency to first openingwithout substantially affecting gating transitions after the channelfirst opens and until it inactivates. To localize the channelcysteine(s) with which MMTS reacts, we generatedNH2- and COOH-terminal deletion mutants and a construct in which all three cysteines in transmembrane regions were substituted. Only theNH2-terminal deletion construct gave rise to currents that activated slowly and displayedMMTS-insensitive kinetics. These results show that theNH2-terminal tail of Kv2.1 participates in transitions leading to activation through interactions involving reduced cysteine(s) that can be modulated from thecytoplasmic phase. 相似文献
974.
Matthew W. Pitts Mariclair A. Reeves Ann C. Hashimoto Ashley Ogawa Penny Kremer Lucia A. Seale Marla J. Berry 《The Journal of biological chemistry》2013,288(36):26121-26134
Selenium is an essential trace element that is co-translationally incorporated into selenoproteins in the form of the 21st amino acid, selenocysteine. This class of proteins largely functions in oxidation-reduction reactions and is critically involved in maintaining proper redox balance essential to health. Selenoprotein M (SelM) is a thioredoxin-like endoplasmic reticulum-resident protein that is highly expressed in the brain and possesses neuroprotective properties. In this study, we first assessed the regional pattern of SelM expression in the mouse brain to provide insights into the potential functional implications of this protein in physiology and behavior. Next, we generated transgenic mice with a targeted deletion of the SelM gene and subjected them to a battery of neurobehavioral tests to evaluate motor coordination, locomotion, and cognitive function in comparison with wild-type controls. Finally, these mice were tested for several measures of metabolic function and body composition. Our results show that SelM knock-out (KO) mice display no deficits in measures of motor coordination and cognitive function but exhibit increased weight gain, elevated white adipose tissue deposition, and diminished hypothalamic leptin sensitivity. These findings suggest that SelM plays an important role in the regulation of body weight and energy metabolism. 相似文献
975.
Minirhizotrons were used to assess the effects of soil insect suppression on the demography of peach fine roots (<1 mm diameter) over two growing seasons. The experiment was conducted at the USDA–ARS Appalachian Fruit Research Station in Kearneysville, WV, USA using six 15‐year‐old peach trees. Clear butyrate minirhizotrons were installed beneath each tree in April 1996. Soil drench treatments were applied around individual minirhizotron tubes at monthly intervals and consisted of 1 L of water or 250 µL of a broad‐spectrum insecticide in 1 L of water. Roots were videotaped at 2‐ to 4‐week intervals during the 1996 and 1997 growing seasons. Insecticide application was associated with a significant increase in fine root longevity: the median lifespans of insecticide‐treated roots were 46–125 d longer than those of control roots. In addition, the development of brown pigmentation was significantly delayed in insecticide‐treated roots. Insecticide application did not appear to increase soil fertility, as accumulation of NO3–, NH4+, and PO42‐ on mixed bed ion‐exchange resin was similar in treated and untreated soil. These results suggest that interactions with below‐ground insects can significantly influence root longevity and may alter the rate at which roots undergo developmental changes in anatomy and physiology. 相似文献
976.
977.
Ion-pair reverse-phase high-performance liquid chromatography is a quick and convenient method for obtaining essentially pure preparations of the HMG (high mobility group)-1 and HMG-2 proteins if dithiothreitol is added to the eluted HMG protein fractions to prevent oxidation and their subsequent altered migration on acid-urea polyacrylamide gels. Unexpectedly, we found that this chromatographic separation technique can resolve the oxidized and reduced forms of both HMG-1 and HMG-2 proteins. We show that oxidized HMG-1 and -2 protein subfractions are responsible for some, but by no means all, of the HMG-1 and -2 protein heterogeneity previously reported by Elton and Reeves (2). At least two different HMG-1 protein species (one major and one minor) and at least four different HMG-2 protein species (two major and two minor) are consistently found in fully reduced "enriched" HMG-1 and -2 pig thymus protein preparations. 相似文献
978.
G G Krivi M L Bittner E Rowold E Y Wong K C Glenn K S Rose D C Tiemeier 《The Journal of biological chemistry》1985,260(18):10263-10267
Monoclonal antibodies to Escherichia coli recA protein were prepared, characterized, and used as affinity reagents for the purification of recA and recA:somatostatin fusion proteins. The monoclonal antibodies recognize an antigenic determinant or determinants located between amino acids 260 and 330 of recA. Addition of a fragment of the recA gene coding for these amino acids to an unrelated gene (beta-galactosidase) allowed the resulting beta-galactosidase fusion protein to be recognized by the recA monoclonal antibodies. 相似文献
979.
The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. 总被引:37,自引:0,他引:37
We have determined the domains of the mammalian high mobility group (HMG)I chromosomal proteins necessary and sufficient for binding to the narrow minor groove of stretches of A.T-rich DNA. Three highly conserved regions within each of the known HMG-I proteins is closely related to the consensus sequence T-P-K-R-P-R-G-R-P-K-K. A synthetic oligopeptide corresponding to this consensus "binding domain" (BD) sequence specifically binds to substrate DNA in a manner similar to the intact HMG-I proteins. Molecular Corey-Pauling-Koltun model building and computer simulations employing energy minimization programs to predict structure suggest that the consensus BD peptide has a secondary structure similar to the antitumor and antiviral drugs netropsin and distamycin and to the dye Hoechst 33258. In vitro these ligands, which also preferentially bind to A.T-rich DNA, have been demonstrated to effectively compete with both the BD peptide and the HMG-I proteins for DNA binding. The BD peptide also contains novel structural features such as a predicted Asx bend or "hook" at its amino-terminal end and laterally projecting cationic Arg/Lys side chains or "bristles" which may contribute to the binding properties of the HMG-I proteins. The predicted BD peptide structure, which we refer to as the "A.T-hook," represents a previously undescribed DNA-binding motif capable of binding to the minor groove of stretches of A.T base pairs. 相似文献
980.