全文获取类型
收费全文 | 1956篇 |
免费 | 273篇 |
出版年
2021年 | 35篇 |
2019年 | 17篇 |
2018年 | 22篇 |
2017年 | 26篇 |
2016年 | 43篇 |
2015年 | 64篇 |
2014年 | 52篇 |
2013年 | 60篇 |
2012年 | 87篇 |
2011年 | 88篇 |
2010年 | 69篇 |
2009年 | 67篇 |
2008年 | 73篇 |
2007年 | 76篇 |
2006年 | 60篇 |
2005年 | 82篇 |
2004年 | 70篇 |
2003年 | 68篇 |
2002年 | 61篇 |
2001年 | 66篇 |
2000年 | 65篇 |
1999年 | 48篇 |
1998年 | 32篇 |
1997年 | 34篇 |
1996年 | 18篇 |
1995年 | 26篇 |
1994年 | 24篇 |
1993年 | 36篇 |
1992年 | 50篇 |
1991年 | 28篇 |
1990年 | 40篇 |
1989年 | 51篇 |
1988年 | 31篇 |
1987年 | 41篇 |
1986年 | 42篇 |
1985年 | 35篇 |
1984年 | 38篇 |
1983年 | 22篇 |
1981年 | 21篇 |
1980年 | 19篇 |
1979年 | 26篇 |
1978年 | 23篇 |
1977年 | 20篇 |
1976年 | 20篇 |
1975年 | 19篇 |
1974年 | 31篇 |
1973年 | 32篇 |
1972年 | 26篇 |
1971年 | 20篇 |
1970年 | 16篇 |
排序方式: 共有2229条查询结果,搜索用时 15 毫秒
1.
C D Wolleben R K McPherson J Rulfs G L Johnson T B Miller 《Biochimica et biophysica acta》1987,928(1):98-106
The phosphorylation of glycogen synthase has been studied in freshly isolated adult rat cardiomyocytes. Six peaks of 32P-labeled tryptic peptides are recovered via C-18 high performance liquid chromatography (HPLC) when synthase is immunoprecipitated from 32P-labeled cardiomyocytes and digested with trypsin. When epinephrine treated cells are used as a source of enzyme, the same HPLC profile is obtained with a dramatic enhancement of 32P recovered in two of the HPLC peaks. In vitro phosphorylation of rat heart synthase by cAMP-dependent protein kinase stimulates the conversion of synthase from the I to the D form and results in the recovery of the same tryptic peptides from the C-18 as is the case for synthase derived from cardiomyocytes. Treatment of cAMP-dependent kinase phosphorylated synthase with protein phosphatase-1 leads to a reactivation of the enzyme and a dephosphorylation of the same tryptic peptides that are selectively phosphorylated in epinephrine treated cardiomyocytes. These results are discussed in relation to hormonal control of glycogen metabolism in cardiac tissue. 相似文献
2.
Roger Williams Herbert Axelrod Marie Greene Alexander McPherson 《Journal of Protein Chemistry》1987,6(4):343-352
The binding of pentaammineruthenium (III) to ribonuclease A and B both free and complexed with d(pA)4 has been examined in the crystalline state through the application of X-ray diffraction and difference Fourier techniques. In crystals of native RNase B, the reagent was observed to have many binding sites, some entirely electrostatic in nature and others consistent with coordination to histidine residues. The primary histidine in the latter case was 105 with 119 also partially substituted. In crystals of RNase A+d(pA)4 complex only a single, extremely strong site of substitution was observed, and this was 2.4 Å from the native position of the imidazole ring of histidine 105. Thus, the results of these X-ray diffraction studies appear to be quite consistent with the findings of earlier NMR studies and with the results obtained in crystals of the gene 5 DNA binding protein. 相似文献
3.
4.
5.
Yurii G. Kuznetsov Alexander McPherson 《Microbiology and molecular biology reviews》2011,75(2):268-285
Summary: Atomic force microscopy (AFM) can visualize almost everything pertinent to structural virology and at resolutions that approach those for electron microscopy (EM). Membranes have been identified, RNA and DNA have been visualized, and large protein assemblies have been resolved into component substructures. Capsids of icosahedral viruses and the icosahedral capsids of enveloped viruses have been seen at high resolution, in some cases sufficiently high to deduce the arrangement of proteins in the capsomeres as well as the triangulation number (T). Viruses have been recorded budding from infected cells and suffering the consequences of a variety of stresses. Mutant viruses have been examined and phenotypes described. Unusual structural features have appeared, and the unexpectedly great amount of structural nonconformity within populations of particles has been documented. Samples may be imaged in air or in fluids (including culture medium or buffer), in situ on cell surfaces, or after histological procedures. AFM is nonintrusive and nondestructive, and it can be applied to soft biological samples, particularly when the tapping mode is employed. In principle, only a single cell or virion need be imaged to learn of its structure, though normally images of as many as is practical are collected. While lateral resolution, limited by the width of the cantilever tip, is a few nanometers, height resolution is exceptional, at approximately 0.5 nm. AFM produces three-dimensional, topological images that accurately depict the surface features of the virus or cell under study. The images resemble common light photographic images and require little interpretation. The structures of viruses observed by AFM are consistent with models derived by X-ray crystallography and cryo-EM. 相似文献
6.
Kathryn S. Evans Janneke Wit Lewis Stevens Steffen R. Hahnel Briana Rodriguez Grace Park Mostafa Zamanian Shannon C. Brady Ellen Chao Katherine Introcaso Robyn E. Tanny Erik C. Andersen 《PLoS pathogens》2021,17(3)
Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes. 相似文献
7.
8.
9.
10.
Nerve growth factor treatment or cAMP elevation reduces Ca2+/calmodulin-dependent protein kinase III activity in PC12 cells 总被引:3,自引:0,他引:3
A C Nairn R A Nichols M J Brady H C Palfrey 《The Journal of biological chemistry》1987,262(29):14265-14272
Ca2+/calmodulin-dependent protein kinase III (Ca2+/CaM kinase III) phosphorylates a protein of Mr = 100,000 (the 100-kDa protein), a major substrate for Ca2+/CaM-dependent protein phosphorylation found in many mammalian tissues and cell lines (Nairn, A.C., Baghat, B., and Palfrey, H.C. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7939-7943). Treatment of PC12 cells with nerve growth factor (NGF) or forskolin resulted in a decrease in the depolarization-dependent phosphorylation of the 100-kDa protein in intact cells and in a decrease in the Ca2+/CaM-dependent phosphorylation of the 100-kDa protein in cytosolic extracts. In experiments using cytosolic extracts, the initial effect of NGF on the phosphorylation of the 100-kDa protein was observed in less than 1 h, was maximal (70% decrease) after 12 h, and began to recover after 24 h. The effect of forskolin was more rapid and the maximal effect was greater (90-95% decrease). Decreased Ca2+/CaM kinase III activity was also found in PC12 cells treated with epidermal growth factor, 2-chloroadenosine plus isobutylmethylxanthine, or dibutyryl cAMP. The effect of forskolin did not reverse unless it was removed. Cycloheximide blocked the recovery of Ca2+/CaM kinase III activity observed following the removal of forskolin but did not affect the ability of forskolin to reduce kinase activity. Short-term treatment with phorbol ester had little effect on Ca2+/CaM kinase III activity; long-term treatment with phorbol ester, which results in the disappearance of enzymatically detectable protein kinase C, had no effect on the ability of NGF or 2-chloroadenosine to reduce Ca2+/CaM kinase III activity. The level of the 100-kDa protein as determined by immunological techniques was not changed by any treatment. These results suggested that the effect of treatment of PC12 cells with NGF or forskolin was to reduce the level of Ca2+/CaM kinase III per se. 相似文献