全文获取类型
收费全文 | 351篇 |
免费 | 47篇 |
出版年
2021年 | 5篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2016年 | 3篇 |
2015年 | 10篇 |
2014年 | 9篇 |
2013年 | 4篇 |
2012年 | 10篇 |
2011年 | 17篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 10篇 |
2007年 | 15篇 |
2006年 | 15篇 |
2005年 | 16篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 8篇 |
2001年 | 12篇 |
2000年 | 14篇 |
1999年 | 9篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1994年 | 3篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 3篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1980年 | 5篇 |
1979年 | 16篇 |
1978年 | 10篇 |
1977年 | 4篇 |
1976年 | 11篇 |
1975年 | 11篇 |
1974年 | 12篇 |
1973年 | 9篇 |
1972年 | 5篇 |
1971年 | 7篇 |
1970年 | 3篇 |
1969年 | 5篇 |
1968年 | 8篇 |
1966年 | 4篇 |
1965年 | 2篇 |
1890年 | 2篇 |
排序方式: 共有398条查询结果,搜索用时 15 毫秒
101.
A nuclear poly(A) polymerase has been isolated from oviducts of immature quails. It could be purified 4300-fold. The enzyme depends specifically on ATP as substrate and requires Mg2+. The most effective primer for the enzyme is a polynucleotide, isolated from oviduct tissue. A poly(A) sequence to a maximum of 60 AMP residues is covalently linked per primer molecule. The poly(A)-rich product of the enzymatic reaction can be annealed to oligo(dT)-cellulose. The purest fraction does not contain any detectable poly(A)-degrading enzyme activity. Only very low activities of RNA polymerase are present. The poly(A polymerase activity in the assay with ATP is reduced by the ATP analogue, beta, lambda-ATP-methylene-diphosphonate. Both K-m and V are lowered. The ATP analogue is incorporated to a smaller extent into the poly(A) sequence, synthesized by the enzyme. Several other analogues of adenine, adenine nucleosides and adenine nucleotides are without effect on the enzymatic reaction. By these properties poly(A) polymerase can be distinguished from RNA polymerases form I and form II, isolated from the same tissue. Actinomycin D and alpha-amanitin failed to inhibit poly(A) polymerase activity. The activity of poly(A) polymerase has been determined during primary stimulation with the estrogen analogue diethylstilbestrol (daily injection for 5 days), after withdrawal of the hormone for 17 days and after secondary stimulation with the hormone analogue. The enzyme activity does not change during primary stimulation, withdrawal of the hormone or secondary stimulation. However the activity of a poly(A) degrading enzyme, localized in the nucleus, is reduced in oviducts from hormone-treated quails. 相似文献
102.
Joern E. Schmitz Zhong-Min Ma Emily A. Hagan Andrew B. Wilks Kathryn L. Furr Caitlyn H. Linde Roland C. Zahn Jason M. Brenchley Christopher J. Miller Sallie R. Permar 《Journal of virology》2012,86(20):11380-11385
Simian immunodeficiency virus (SIV) infection of natural hosts is characterized by nonpathogenic chronic viremia, maintenance of gastrointestinal epithelial barrier integrity, and low numbers of target cells. Assessment of cell-associated virus load in T cell subsets in multiple anatomic compartments of chronically SIV-infected sabeus African green monkeys (AGMs) revealed that gastrointestinal memory CD4+ T lymphocytes are a major source of cell-associated virus and a significant contributor to SIV viremia in AGMs. 相似文献
103.
Orthwein A Zahn A Methot SP Godin D Conticello SG Terada K Di Noia JM 《The EMBO journal》2012,31(3):679-691
The enzyme activation-induced deaminase (AID) deaminates deoxycytidine at the immunoglobulin genes, thereby initiating antibody affinity maturation and isotype class switching during immune responses. In contrast, off-target DNA damage caused by AID is oncogenic. Central to balancing immunity and cancer is AID regulation, including the mechanisms determining AID protein levels. We describe a specific functional interaction between AID and the Hsp40 DnaJa1, which provides insight into the function of both proteins. Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. Conversely, DnaJa1, but not DnaJa2, depletion reduces AID levels, stability and isotype switching. In vivo, DnaJa1-deficient mice display compromised response to immunization, AID protein and isotype switching levels being reduced by half. Moreover, DnaJa1 farnesylation is required to maintain, and farnesyltransferase inhibition reduces, AID protein levels in B cells. Thus, DnaJa1 is a limiting factor that plays a non-redundant role in the functional stabilization of AID. 相似文献
104.
105.
Substantial changes of cellular iron homeostasis during megakaryocytic differentiation of K562 cells
We investigated the remodeling of iron metabolism during megakaryocytic development of K562 cells. Differentiation was successfully verified by increase of the megakaryocytic marker CD61 and concomitant decrease of the erythroid marker γ-globin. The reduction of erythroid properties was accompanied by changes in the cellular iron content and in the expression of proteins regulating cellular iron homeostasis. Independent of available inorganic or transferrin-bound extracellular iron, total intracellular iron increases while the iron-to-protein ratio decreases. The iron exporter ferroportin is downregulated within 1-6 h, followed by downregulation of transferrin receptor-1 (TfR1) and ferritin heavy chain (H-ferritin) mainly after 24-48 h. The hemochromatosis protein-1, a ligand of TfR1, peaked after 24 h. All effects were independent of iron supply with the exception of H-ferritin, which was restored by excess iron. While alterations of CD61, TfR1 and ferritin expression were revoked by a protein kinase C inhibitor, downregulation of ferroportin remained unaffected. 相似文献
106.
107.
J?rn E. Schmitz Roland C. Zahn Charles R. Brown Melisa D. Rett Ming Li Haili Tang Sarah Pryputniewicz Russell A. Byrum Amitinder Kaur David C. Montefiori Jonathan S. Allan Simoy Goldstein Vanessa M. Hirsch 《PLoS pathogens》2009,5(12)
African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIVagmVer90 to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms. 相似文献
108.
We describe the synthesis of eight novel C-nucleosides in which the nucleobases are replaced by biphenyl residues that carry one or two electron donor (-OCH3,-NH2) or acceptor (-NO2) functional groups in the distal ring. These C-nucleosides were synthesized convergently and in high yields from a common bromophenyl-C-nucleoside precursor via Suzuki coupling with the respective boronic acids or esters. These nucleosides were subsequently converted into the corresponding phosphoramidite building blocks and efficiently incorporated into oligodeoxynucleotides by standard phosphoramidite chemistry. 相似文献
109.
Monique Juergens Claudia Paetsch Ilona Krämer Marc Zahn Frank Rabenstein Jörg Schondelmaier Edgar Schliephake Rod Snowdon Wolfgang Friedt Frank Ordon 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(4):735-744
The aphid transmitted Turnip yellows virus (TuYV) has become a serious pathogen in many rapeseed (Brassica napus L.) growing areas. Three-years’ field trials were carried out to get detailed information on the genetics of TuYV resistance
derived from the resynthesised B. napus line ‘R54’ and to develop closely linked markers. F1 plants and segregating doubled-haploid (DH) populations derived from crosses to susceptible cultivars were analysed using
artificial inoculation with virus-bearing aphids, followed by DAS-ELISA. Assuming a threshold of E
405 = 0.1 in ELISA carried out in December, the results led to the conclusion that pre-winter inhibition of TuYV is inherited
in a monogenic dominant manner. However, the virus titre in most resistant lines increased during the growing period, indicating
that the resistance is incomplete and that the level of the virus titre is influenced by environmental factors. Bulked-segregant
marker analysis for this resistance locus identified two closely linked SSR markers along with six closely linked and three
co-segregating AFLP markers. Two AFLP markers were converted into co-dominant STS markers, facilitating efficient marker-based
selection for TuYV resistance. Effective markers are particularly valuable with respect to breeding for TuYV resistance, because
artificial inoculation procedures using virus-bearing aphids are extremely difficult to integrate into practical rapeseed
breeding programs. 相似文献
110.
Gunther Zischinsky Frank Osterkamp Doerte Vossmeyer Grit Zahn Dirk Scharn Ariane Zwintscher Roland Stragies 《Bioorganic & medicinal chemistry letters》2010,20(1):380-382
Previous research within our laboratories identified the 3-hydroxypyrrolidine scaffold 1 as a new and selective integrin α5β1 inhibitor class which was designed for local administration. Herein the discovery of new orally available integrin α5β1 inhibitor scaffolds for potential systemic treatment is described. 相似文献