全文获取类型
收费全文 | 257篇 |
免费 | 21篇 |
专业分类
278篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 7篇 |
2018年 | 5篇 |
2017年 | 7篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 14篇 |
2013年 | 18篇 |
2012年 | 18篇 |
2011年 | 11篇 |
2010年 | 16篇 |
2009年 | 8篇 |
2008年 | 14篇 |
2007年 | 11篇 |
2006年 | 18篇 |
2005年 | 9篇 |
2004年 | 10篇 |
2003年 | 4篇 |
2002年 | 7篇 |
2001年 | 9篇 |
2000年 | 6篇 |
1999年 | 12篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1971年 | 2篇 |
1922年 | 1篇 |
排序方式: 共有278条查询结果,搜索用时 0 毫秒
61.
Marine derivatives are of great pharmaceutical interest as inhibitory compound and search of bioactive compounds from Marine
organism which is relatively new to medicinal chemistry. Our main aim in the study is to screen possible inhibitors against
CCR5 which acts as co-receptor M-tropic HIV-1, through virtual screening of 122 Marine derived compounds from various
organisms known to have biological activity. Homology Model of CCR5 was constructed using MODELLER and the Model was energy
minimized and validated using PROCHECK to obtain a stable structure, which was further used for virtual screening of Marine
derived compounds through molecular Docking studies using GOLD. The Docked complexes were validated and Enumerated based on
the GOLD Scoring function to pick out the best Marine inhibitor based on GOLD score. Thus from the entire 122 Marine
compounds which were Docked, we got best 4 of them with optimal GOLD Score.
(LAMIVUDINE: 45.0218, BATZELLINE-D: 44.3852.ACYCLOVIR: 43.1362 and THIIOACETAMIDE: 42.7412) Further the Complexes were analyzed
through LIGPLOT for their interaction for the 4 best docked Marine compounds. Thus from the Complex scoring and binding ability its
deciphered that these Marine compounds could be promising inhibitors for M-tropic HIV-1 using CCR5 as Drug target yet pharmacological
studies have to confirm it. 相似文献
62.
Variations among cell lines in the synthesis of sphingolipids in de novo and recycling pathways 总被引:1,自引:0,他引:1
There are several pathways for the incorporation of sugars into
glycosphingolipids (GSL). Sugars can be added to ceramide that contains
sphinganine (dihydrosphingosine) synthesized de novo (pathway 1), to
ceramide synthesized from sphingoid bases produced by hydrolysis of
sphingolipids (pathway 2), and into GSL recycling from the endosomal
pathway through the Golgi (pathway 3). We reported previously the
surprising observation that SW13 cells, a human adrenal carcinoma cell
line, synthesize most of their GSL in pathway 2. We now present data on the
synthesis of GSL in four additional cell lines. Approximately 90% of sugar
incorporation took place in pathway 2, and 10% or less in pathway 1, in
human foreskin fibroblasts and NB41A3 neuroblastoma cells. In contrast,
approximately 50-90% of sugar incorporation took place in pathway 1 in
C2C12 myoblasts. The C2C12 cells divide more rapidly and synthesize 10-14
times as much GSL as the other three cell lines. In C6 glioma cells,
approximately 30% of sugar incorporation occurred in pathway 1 and 60% in
pathway 2. There was no relation between the utilization of pathways for
GSL and sphingomyelin synthesis in foreskin fibroblasts and C2C12 cells. In
both cells pathways 1 and 2 each accounted for 50% of incorporation of
choline into sphingomyelin. In five of the six cell lines that we have
studied, most GSL synthesis takes place in pathway 2. We suggest that when
the need for synthesis is relatively low, as in slowly dividing cells, GSL
are synthesized predominantly from sphingoid bases salvaged from the
hydrolytic pathway. When cells are dividing more rapidly, the need for
increased synthesis is met by upregulating the de novo pathway.
相似文献
63.
Localization of the human oestrogen receptor gene to chromosome 6q24----q27 by in situ hybridization 总被引:9,自引:0,他引:9
The oestrogen receptor gene (ER) was mapped by in situ hybridization. Using a human cDNA probe containing the coding sequence for the oestrogen receptor, the gene was localized to 6q24----q27. 相似文献
64.
Fernandez-Martinez J Phillips J Sekedat MD Diaz-Avalos R Velazquez-Muriel J Franke JD Williams R Stokes DL Chait BT Sali A Rout MP 《The Journal of cell biology》2012,196(4):419-434
The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ~600-kD heptameric Nup84 complex, to a precision of ~1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain-mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC's interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution. 相似文献
65.
Tracy M. Rout Stephen M. Jackson Dalene Adam Jacqui Diggins Eve McDonald-Madden Nicola J. Mitchell Terry V. Walshe 《Austral ecology》2023,48(4):803-821
Ex situ (‘off-site’) management refers to keeping species in artificial conditions away from their natural habitat and includes captive breeding facilities, botanical gardens and seed banks. There is scope for ex situ programmes to be more commonly used for supplementing or establishing wild populations. However, undertaking ex situ management comes with risks, costs and uncertainties, which must be assessed in the context of available in situ (‘on-site’) management options. The PACES (Planning and Assessment for Conservation through Ex situ management) tool tailors the principles of structured decision-making to the specific problem of assessing and comparing ex situ and in situ management options. We applied the PACES tool to the mahogany glider (Petaurus gracilis), a threatened arboreal marsupial endemic to north Queensland, Australia. Through an expert elicitation process, we predicted the likely benefits of an ex situ and two in situ management options, as compared to a baseline ‘do-nothing’ scenario. The ‘in situ plus’ alternative (where extra resources are dedicated to in situ management) was predicted to result in the largest population increase according to the participants' best estimates. However, this benefit came at a much larger cost than the ex situ alternative, and without the benefit of an ex situ insurance population. The PACES tool assessment allowed the Mahogany Glider Recovery Team to document and plan the financial costs, risks and benefits of potential future management options for the mahogany glider, laying a transparent basis for future assessment and decision-making. 相似文献
66.
In addition to its high affinity for antibody Fc domains, staphylococcal Protein A has been shown to bind certain Fab domains. We investigated this in order to develop a small, recombinant Protein A-binding alternative to immunoglobulin G (IgG) from nanobodies, single-domain antibodies derived from a camelid variant IgG’s variable region. We engineered a nanobody with affinity solely for Protein A as well as a dimerized version of higher affinity for typical multidomain Protein A constructs. Because this recombinant nanobody can be immobilized using a cleavable crosslinker, it has proven to be suitable for the isolation and mild elution of protein complexes in native conditions. 相似文献
67.
M A Barnett V J Buckle E P Evans A C Porter D Rout A G Smith W R Brown 《Nucleic acids research》1993,21(1):27-36
Cloned human telomeric DNA can integrate into mammalian chromosomes and seed the formation of new telomeres. This process occurs efficiently in three established human cell lines and in a mouse embryonic stem cell line. The newly seeded telomeres appear to be healed by telomerase. The seeding of new telomeres by cloned telomeric DNA is either undetectable or very inefficient in non-tumourigenic mouse or human somatic cell lines. The cytogenetic consequences of the seeding of new telomeres include large chromosome truncations but most of the telomere seeding events occur close to the pre-existing ends of natural chromosomes. 相似文献
68.
A highly efficient protocol for in vitro regeneration of an indigenous, endangered medicinal plant Celastrus paniculatus was achieved using nodal explants. Murashige and Skoog (MS) basal medium supplemented with 0.5 mg/L 6-benzylaminopurine (BAP) and 0.1 mg/L naphthaleneacetic acid (NAA) showed maximum percentage of shoot multiplication (83.4%) with 8.2 shoots/explants. Maximum rooting of 73.3% with 4.8 roots/shoot was achieved on half-strength MS media supplemented with 0.5 mg/L indole-3-acetic acid (IAA) and the percentage of survival was 91% after acclimatization. Random amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) marker study confirmed genetic stability for in vitro raised explants by showing 100% monomorphism. High multiplication rate associated with genetic stability ensure the efficacy of the present in vitro clonal propagation protocol of this important medicinal plant species. 相似文献
69.
Understanding the genetic diversity, extent and distribution of variant forms of Plasmodium vivax parasites is crucial in the development of effective control measures and in Orissa, a hyperendemic state in the eastern part of India, the polymorphic nature of P. vivax isolates is largely lacking. The result of the study analyzing two highly polymorphic single copy genes for P. vivax circumsporozoite protein (pvcs) and P. vivax merozoite surface protein 3α (pvmsp3α) shows that the parasite population is highly heterogenous (33 distinct genotype from 35 isolates) in Orissa. However, the observation of the multiplicity of infection value of 1.34 and high frequency distribution of certain genotype with respect to individual marker (the VK247b allele with a frequency of 0.37; VK210e with 0.25 and VK210c with 0.14) suggests that the parasite population are likely to be under selective pressure and may either be due to preferential production of sporozoites carrying these variants in the available anopheline mosquito species of the state or selection of particular genotypes by host immune pressure. Moreover, although P. vivax in South-East Asia indicates an overall predominance of VK210 which is thought to be the best adapted variant of pvcs repeat type, the almost equal prevalence of both repeat type of pvcs; VK210 and VK247 in the present study is unexpected and needs further study for clarification. 相似文献
70.
Biodegradation of chlorpyrifos by bacterial consortium isolated from agriculture soil 总被引:2,自引:0,他引:2
C Sasikala S Jiwal P Rout M Ramya 《World journal of microbiology & biotechnology》2012,28(3):1301-1308
Organophosphorous pesticides are widely used in agriculture to control major insect pests. Chlorpyrifos is one of the major
organophosphorous pesticides which is used to control insects including termites, beetles. The widespread use of these pesticides
is hazardous to the environment and also toxic to mammals, thus it is essential to remove the same from the environment. From
the chlorpyrifos contaminated soil nine morphologically different bacterial strains, one actinomycete and two fungal strains
were isolated. Among those isolates four bacterial strains which were more efficient were developed as consortium. The four
bacterial isolates namely Pseudomonas putida (NII 1117), Klebsiella sp., (NII 1118), Pseudomonas stutzeri (NII 1119), Pseudomonas aeruginosa (NII 1120) present in the consortia were identified on the basis of 16S rDNA analysis. The intracellular fractions of the
consortium exhibited more organophosphorus hydrolase activity (0.171 ± 0.003 U/mL/min). The degradation studies were carried
out at neutral pH and temperature 37°C with chlorpyrifos concentration 500 mg L−1. LC-mass spectral analysis showed the presence of metabolites chlopyrifos-oxon and Diethylphosphorothioate. These results
highlight an important potential use of this consortium for the cleanup of chlorpyrifos contaminated pesticide waste in the
environment. 相似文献