全文获取类型
收费全文 | 3507篇 |
免费 | 404篇 |
国内免费 | 1篇 |
出版年
2021年 | 49篇 |
2020年 | 29篇 |
2019年 | 38篇 |
2018年 | 29篇 |
2017年 | 37篇 |
2016年 | 68篇 |
2015年 | 102篇 |
2014年 | 132篇 |
2013年 | 138篇 |
2012年 | 164篇 |
2011年 | 191篇 |
2010年 | 90篇 |
2009年 | 85篇 |
2008年 | 126篇 |
2007年 | 140篇 |
2006年 | 134篇 |
2005年 | 116篇 |
2004年 | 122篇 |
2003年 | 120篇 |
2002年 | 109篇 |
2001年 | 130篇 |
2000年 | 115篇 |
1999年 | 100篇 |
1998年 | 43篇 |
1997年 | 50篇 |
1996年 | 45篇 |
1995年 | 42篇 |
1994年 | 27篇 |
1993年 | 29篇 |
1992年 | 92篇 |
1991年 | 84篇 |
1990年 | 49篇 |
1989年 | 77篇 |
1988年 | 57篇 |
1987年 | 68篇 |
1986年 | 38篇 |
1985年 | 44篇 |
1984年 | 48篇 |
1983年 | 41篇 |
1982年 | 27篇 |
1981年 | 37篇 |
1979年 | 35篇 |
1978年 | 40篇 |
1977年 | 38篇 |
1976年 | 41篇 |
1975年 | 37篇 |
1974年 | 40篇 |
1973年 | 27篇 |
1972年 | 49篇 |
1971年 | 35篇 |
排序方式: 共有3912条查询结果,搜索用时 15 毫秒
991.
D. Price 《BMJ (Clinical research ed.)》1997,315(7121):1479-1480
992.
993.
994.
John H. Price 《BMJ (Clinical research ed.)》1957,2(5053):1111-1112
995.
Recombinant bovine cardiac sodium-calcium exchange (NCX1) in a baculovirus construct was used to infect cabbage looper larvae (Trichoplusia ni). Infected larvae were homogenized and larvae membrane vesicles were purified. Western blot analysis indicated the presence of recombinant NCX1 protein in vesicles from infected larvae but not in controls. Vesicles from infected larvae expressed high levels of NCX1 activity (1.7 nmol Ca2+/mg protein/s) while vesicles from control larvae had no activity. NCX1 in larvae vesicles was bidirectional. Kinetic analysis yielded a Vmax of 3.6 nmol Ca2+/mg protein/s and a Km for Ca of 4.2 microM. NCX1 activity was inhibited by the exchange inhibitory peptide with an IC50 of 4 microM. These data demonstrate a novel and efficient method for the expression of large amounts of active recombinant NCX1 protein that has general application for expression and analysis of recombinant membrane proteins. 相似文献
996.
Characterization of the solution properties of Pichia farinosa killer toxin using PGSE NMR diffusion measurements 总被引:1,自引:1,他引:0
William S. Price Fumihiko Tsuchiya Chise Suzuki Yoji Arata 《Journal of biomolecular NMR》1999,13(2):113-117
The solution behaviour with respect to pH and NaCl concentration of the tertiary structure and propensity for aggregation of salt- mediated killer toxin (SMKT) from Pichia farinosa was examined using pulsed-gradient spin-echo NMR diffusion measurements. It was found that in 0.15m NaCl the tertiary structure of SMKT was constant below pH 5.0, with the native SMKT existing as an unaggregated heterodimer containing the -subunit in a compactly folded form. However, above pH 5.0 the -subunit dissociated and lost its compact structure, becoming a random coil with an 37% increase in effective hydrodynamic radius. To determine the effects of NaCl concentration on the tertiary structure of SMKT, diffusion measurements were performed at pH 3.5 and NaCl concentrations up to 2M. Both the tertiary structure and aggregation state of SMKT were found to be insensitive to the salt concentration which indicates that the activity of the toxin is not a direct result of salt–protein interactions. 相似文献
997.
Different species of leech vary greatly in body size but all have 32 body segments. It is unclear how the development of
this precise number of segments is regulated, although it is known that the teloblasts of the early leech embryo initially
produce more than the required numbers of segment founder cells (blast cells). We used fluorescent dextrans to show that the
M teloblast of the Helobdella robusta embryo produces a variable number of additional (supernumerary) cells. These cells fail to enter the germinal band (which
contains cells of all lineages and gives rise to the adult leech), but detach from its posterior end and disappear. Our observations
suggest that some suffer an increase in membrane permeability while others fuse with the M teloblasts, but that they do not
undergo apoptosis. The supernumerary cells of different lineages detach from the germinal band at different times, suggesting
that detachment is not triggered by a global signal acting simultaneously on all lineages. We tested the hypothesis that the
elimination of the supernumerary m blast cells results from a requirement of m blast cells for close interactions with cells
of the other lineages for their survival, a condition that would not be achieved by the last-born m blast cells that fail
to enter the germinal band. We cultured isolated M teloblasts and found that they do produce blast cells that themselves divide,
indicating that cells of the M lineage can survive in the absence of any interactions with cells of the other lineages.
Received: 17 August 1998 / Accepted: 20 November 1998 相似文献
998.
Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function 总被引:21,自引:0,他引:21
Lee B Sharron M Blanpain C Doranz BJ Vakili J Setoh P Berg E Liu G Guy HR Durell SR Parmentier M Chang CN Price K Tsang M Doms RW 《The Journal of biological chemistry》1999,274(14):9617-9626
The chemokine receptor CCR5 is the major coreceptor for R5 human immunodeficiency virus type-1 strains. We mapped the epitope specificities of 18 CCR5 monoclonal antibodies (mAbs) to identify domains of CCR5 required for chemokine binding, gp120 binding, and for inducing conformational changes in Env that lead to membrane fusion. We identified mAbs that bound to N-terminal epitopes, extracellular loop 2 (ECL2) epitopes, and multidomain (MD) epitopes composed of more than one single extracellular domain. N-terminal mAbs recognized specific residues that span the first 13 amino acids of CCR5, while nearly all ECL2 mAbs recognized residues Tyr-184 to Phe-189. In addition, all MD epitopes involved ECL2, including at least residues Lys-171 and Glu-172. We found that ECL2-specific mAbs were more efficient than NH2- or MD-antibodies in blocking RANTES or MIP-1beta binding. By contrast, N-terminal mAbs blocked gp120-CCR5 binding more effectively than ECL2 mAbs. Surprisingly, ECL2 mAbs were more potent inhibitors of viral infection than N-terminal mAbs. Thus, the ability to block virus infection did not correlate with the ability to block gp120 binding. Together, these results imply that chemokines and Env bind to distinct but overlapping sites in CCR5, and suggest that the N-terminal domain of CCR5 is more important for gp120 binding while the extracellular loops are more important for inducing conformational changes in Env that lead to membrane fusion and virus infection. Measurements of individual antibody affinities coupled with kinetic analysis of equilibrium binding states also suggested that there are multiple conformational states of CCR5. A previously described mAb, 2D7, was unique in its ability to effectively block both chemokine and Env binding as well as coreceptor activity. 2D7 bound to a unique antigenic determinant in the first half of ECL2 and recognized a far greater proportion of cell surface CCR5 molecules than the other mAbs examined. Thus, the epitope recognized by 2D7 may represent a particularly attractive target for CCR5 antagonists. 相似文献
999.
Nuclear accumulation of truncated atrophin-1 fragments in a transgenic mouse model of DRPLA 总被引:19,自引:0,他引:19
Schilling G Wood JD Duan K Slunt HH Gonzales V Yamada M Cooper JK Margolis RL Jenkins NA Copeland NG Takahashi H Tsuji S Price DL Borchelt DR Ross CA 《Neuron》1999,24(1):275-286
Dentatorubral and pallidoluysian atrophy (DRPLA) is a member of a family of progressive neurodegenerative diseases caused by polyglutamine repeat expansion. Transgenic mice expressing full-length human atrophin-1 with 65 consecutive glutamines exhibit ataxia, tremors, abnormal movements, seizures, and premature death. These mice accumulate atrophin-1 immunoreactivity and inclusion bodies in the nuclei of multiple populations of neurons. Subcellular fractionation revealed 120 kDa nuclear fragments of mutant atrophin-1, whose abundance increased with age and phenotypic severity. Brains of DRPLA patients contained apparently identical 120 kDa nuclear fragments. By contrast, mice overexpressing atrophin-1 with 26 glutamines were phenotypically normal and did not accumulate the 120 kDa fragments. We conclude that the evolution of neuropathology in DRPLA involves proteolytic processing of mutant atrophin-1 and nuclear accumulation of truncated fragments. 相似文献
1000.
Price DM Chik CL Terriff D Weller J Humphries A Carter DA Klein DC Ho AK 《FEBS letters》2004,577(1-2):220-226
The norepinephrine-driven increase in mitogen-activated protein kinase (MAPK) activity is part of the mechanism that regulates arylalkylamine N-acetyltransferase (AA-NAT) activity in the rat pineal gland. We now report a marked nocturnal increase in the expression of a MAPK phosphatase, MAP kinase phosphatase-1 (MKP-1), that was blocked by maintaining animals in constant light or treatment with propranolol. MKP-1 expression was regulated by norepinephrine acting through both alpha- and beta-adrenergic receptors. These results establish a nocturnal increase in pineal MKP-1 expression that is under the control of a photoneural system. Because substrates of MKP-1 can influence AA-NAT activity, our findings suggest the involvement of MKP-1 in the regulation of the nocturnal AA-NAT signal. 相似文献