全文获取类型
收费全文 | 272篇 |
免费 | 25篇 |
国内免费 | 1篇 |
专业分类
298篇 |
出版年
2023年 | 1篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 6篇 |
2015年 | 10篇 |
2014年 | 9篇 |
2013年 | 7篇 |
2012年 | 9篇 |
2011年 | 18篇 |
2010年 | 11篇 |
2009年 | 17篇 |
2008年 | 13篇 |
2007年 | 16篇 |
2006年 | 15篇 |
2005年 | 13篇 |
2004年 | 9篇 |
2003年 | 13篇 |
2002年 | 7篇 |
2001年 | 11篇 |
2000年 | 10篇 |
1999年 | 14篇 |
1998年 | 14篇 |
1997年 | 12篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 2篇 |
排序方式: 共有298条查询结果,搜索用时 0 毫秒
41.
Carlos Frazão Francisco J. Enguita Ricardo Coelho George M. Sheldrick José A. Navarro Manuel Hervás Miguel A. De la Rosa Maria Arménia Carrondo 《Journal of biological inorganic chemistry》2001,6(3):324-332
The crystal structure of low-potential cytochrome c549, an extrinsic component of the photosystem II (PS II) from Synechocystis sp. PCC 6803, was obtained directly from single-wavelength 1.21 A resolution diffraction data. This is the first monodomain bis-histidinyl monoheme cytochrome c to be structurally characterized. The extended N-terminal region of c549 builds up a two-strand antiparallel beta-sheet in a hairpin motif, which extends through two molecules owing to crystal packing. Both peptide termini are involved in crystal contacts, which may explain their protrusion out of the globular fold. The C-terminus is preceded by a 9 A-long hydrophobic finger extending from a positively charged base and could be involved in PSII interactions, as well as a protruding negative patch built by a set of conserved acidic residues among c549 sequences. 相似文献
42.
Marmoset phylogenetics, conservation perspectives, and evolution of the mtDNA control region 总被引:3,自引:1,他引:2
Tagliaro CH; Schneider MP; Schneider H; Sampaio IC; Stanhope MJ 《Molecular biology and evolution》1997,14(6):674-684
Marmosets (genus Callithrix) are a diverse group of platyrrhine primates
with 13-15 purported taxa, many of them considered endangered.
Morphological analyses constitute most of the basis for recognition of
these forms as distinct taxa. The purpose of this study was to provide a
molecular view, based on mitochondrial control region sequences, of the
evolutionary history of the marmosets, concomitant with a molecular
phylogenetic perspective on species diversity within the group. An
additional purpose was to provide the first comparative examination of a
complete New World monkey control region sequence with those of other
mammals. The phylogenetic analyses provide convincing support for a split
between the Atlantic forest and Amazonian marmosets, with the inclusion of
the pygmy marmoset (Cebuella pygmaea) at the base of the Amazonian clade.
The earliest branch of the Atlantic forest group was C. aurita. In the
Amazonian group, the analyses do not support the recognition of C.
humeralifer and the recently described C mauesi as distinct taxa. They do,
however, support a clear distinction between C. argentata and a strongly
supported mixed clade of C. humeralifer and C. mauesi. In the Atlantic
forest group, the phylogenetic tree suggests mixing between C. penicillata,
C. kuhli, and possibly C. jacchus. Most of the sequence features
characteristic of other mammal control regions were also evident in
marmosets, with the exception that conserved sequence blocks (CSBs) 2 and 3
were not clearly identifiable. Tandem repeat units often associated with
heteroplasmy in a variety of other mammals were not evident in the marmoset
sequences.
相似文献
43.
C Fraz?o I Bento J Costa C M Soares P Veríssimo C Faro E Pires J Cooper M A Carrondo 《The Journal of biological chemistry》1999,274(39):27694-27701
Aspartic proteinases (AP) have been widely studied within the living world, but so far no plant AP have been structurally characterized. The refined cardosin A crystallographic structure includes two molecules, built up by two glycosylated peptide chains (31 and 15 kDa each). The fold of cardosin A is typical within the AP family. The glycosyl content is described by 19 sugar rings attached to Asn-67 and Asn-257. They are localized on the molecular surface away from the conserved active site and show a new glycan of the plant complex type. A hydrogen bond between Gln-126 and Manbeta4 renders the monosaccharide oxygen O-2 sterically inaccessible to accept a xylosyl residue, therefore explaining the new type of the identified plant glycan. The Arg-Gly-Asp sequence, which has been shown to be involved in recognition of a putative cardosin A receptor, was found in a loop between two beta-strands on the molecular surface opposite the active site cleft. Based on the crystal structure, a possible mechanism whereby cardosin A might be orientated at the cell surface of the style to interact with its putative receptor from pollen is proposed. The biological implications of these findings are also discussed. 相似文献
44.
Maria de Fátima Silva Lopes Ana Lúcia Leitão J.J. Figueiredo Marques Manuel José Teixeira Carrondo Maria Teresa Barreto Crespo 《FEMS microbiology letters》1999,176(2):483-487
The hypothesis of a proteolytic involvement in the extracellular lipase processing of a strain of Lactobacillus plantarum was considered and tested, in vitro assays with acid proteases, cathepsin D and renin revealed that both did affect lipolytic activity positively. In vivo assays with growth in the presence of the protease inhibitors pepstatin, phenylmethylsulfonyl fluoride, transepoxysuccinyl-L-leucylamido-(4-guanidino)butane and ethylenediaminetetraacetic acid showed that ethylenediaminetetraacetic acid did affect the pattern of the proteins that possess lipolytic activity. Therefore, it is suggested that a metalloprotease is involved in the processing of the extracellular lipases of L. plantarum, although other proteases can also be important. 相似文献
45.
Mandenius CF Andersson TB Alves PM Batzl-Hartmann C Björquist P Carrondo MJ Chesne C Coecke S Edsbagge J Fredriksson JM Gerlach JC Heinzle E Ingelman-Sundberg M Johansson I Küppers-Munther B Müller-Vieira U Noor F Zeilinger K 《Alternatives to laboratory animals : ATLA》2011,39(2):147-171
Drug-induced liver injury is a common reason for drug attrition in late clinical phases, and even for post-launch withdrawals. As a consequence, there is a broad consensus in the pharmaceutical industry, and within regulatory authorities, that a significant improvement of the current in vitro test methodologies for accurate assessment and prediction of such adverse effects is needed. For this purpose, appropriate in vivo-like hepatic in vitro models are necessary, in addition to novel sources of human hepatocytes. In this report, we describe recent and ongoing research toward the use of human embryonic stem cell (hESC)-derived hepatic cells, in conjunction with new and improved test methods, for evaluating drug metabolism and hepatotoxicity. Recent progress on the directed differentiation of human embryonic stem cells to the functional hepatic phenotype is reported, as well as the development and adaptation of bioreactors and toxicity assay technologies for the testing of hepatic cells. The aim of achieving a testing platform for metabolism and hepatotoxicity assessment, based on hESC-derived hepatic cells, has advanced markedly in the last 2-3 years. However, great challenges still remain, before such new test systems could be routinely used by the industry. In particular, we give an overview of results from the Vitrocellomics project (EU Framework 6) and discuss these in relation to the current state-of-the-art and the remaining difficulties, with suggestions on how to proceed before such in vitro systems can be implemented in industrial discovery and development settings and in regulatory acceptance. 相似文献
46.
Marieke?Pingen Ramin?Sarrami-Forooshani Annemarie?MJ?Wensing Petra?van Ham Agata?Drewniak Charles?AB?Boucher Teunis?BH?GeijtenbeekEmail author Monique?NijhuisEmail author 《Retrovirology》2014,11(1):113
Background
Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns.As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.Results
In comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5+ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5+ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs.Conclusions
Our data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals.47.
Persistent nuclear ribosomal DNA sequence polymorphism in the Amelanchier agamic complex (Rosaceae) 总被引:5,自引:0,他引:5
Campbell CS; Wojciechowski MF; Baldwin BG; Alice LA; Donoghue MJ 《Molecular biology and evolution》1997,14(1):81-90
Individual plants of several Amelanchier taxa contain many polymorphic
nucleotide sites in the internal transcribed spacers (ITS) of nuclear
ribosomal DNA (nrDNA). This polymorphism is unusual because it is not
recent in origin and thus has resisted homogenization by concerted
evolution. Amelanchier ITS sequence polymorphism is hypothesized to be the
result of gene flow between two major North American clades resolved by
phylogenetic analysis of ITS sequences. Western North American species plus
A. humilis and A. sanguinea of eastern North America form one clade (A),
and the remaining eastern North American Amelanchier make up clade B. Five
eastern North American taxa are polymorphic at many of the nucleotide sites
where clades A and B have diverged and are thought to be of hybrid origin,
with A. humilis or A. sanguinea as one parent and various members of clade
B as the other parent. Morphological evidence suggests that A. humilis is
one of the parents of one of the polymorphic taxa, a microspecies that we
refer to informally as A. "erecta." Sequences of 21 cloned copies of the
ITS1- 5.8S gene-ITS2 region from one A. "erecta" individual are identical
to A. humilis sequence or to the clade B consensus sequence, or they are
apparent recombinants of A. humilis and clade B ITS repeats. Amelanchier
"erecta" and another polymorphic taxon are suspected to be relatively old
because both grow several hundred kilometers beyond the range of one of
their parents. ITS sequence polymorphisms have apparently persisted in
these two taxa perhaps because of polyploidy and/or agamospermy (asexual
seed production), which are prevalent in the genus.
相似文献
48.
JA Nboyine S Boyer D Saville MJ Smith SD Wratten 《New Zealand journal of zoology.》2016,43(4):336-350
The endemic New Zealand ground wētā (Hemiandrus sp. ‘promontorius’) has a Naturally Uncommon conservation status. This is because of the paucity of information on its density and distribution. Here, the biology, density and distribution of a population of this wētā found in and around vineyards in the Awatere Valley, Marlborough was studied. Wētā density was assessed in vineyards, paddocks and shrublands in this valley. Soil moisture, penetration resistance, pH and organic matter were recorded at locations with and without wētā. Wētā density in vineyards was significantly higher than in either paddocks or shrub habitats. In vineyards, the density of this insect was significantly higher under-vines than in the inter-rows. Higher numbers of this wētā were found in moist soils that required lower force to burrow. Females laid an average of 55 eggs between March and April, which hatched in September. These findings highlight the intersection between agriculture and conservation. 相似文献
49.
Bakker MF Verstappen SM Welsing PM Jacobs JW Jahangier ZN van der Veen MJ Bijlsma JW Lafeber FP;Utrecht Arthritis Cohort study group 《Arthritis research & therapy》2011,13(3):R70
Introduction
The aim of this study was to investigate whether serum biomarker levels of C2C, C1,2C, CS846, and CPII can predict the long-term course of disease activity and radiographic progression early in the disease course of rheumatoid arthritis (RA). 相似文献50.
We have broadly defined the DNA regions regulating esterase6 activity in
several life stages and tissue types of D. melanogaster using P-
element-mediated transformation of constructs that contain the esterase6
coding region and deletions or substitutions in 5' or 3' flanking DNA.
Hemolymph is a conserved ancestral site of EST6 activity in Drosophila and
the primary sequences regulating its activity lie between -171 and -25 bp
relative to the translation initiation site: deletion of these sequences
decrease activity approximately 20-fold. Hemolymph activity is also
modulated by four other DNA regions, three of which lie 5' and one of which
lies 3' of the coding region. Of these, two have positive and two have
negative effects, each of approximately twofold. Esterase6 activity is
present also in two male reproductive tract tissues; the ejaculatory bulb,
which is another ancestral activity site, and the ejaculatory duct, which
is a recently acquired site within the melanogaster species subgroup.
Activities in these tissues are at least in part independently regulated:
activity in the ejaculatory bulb is conferred by sequences between -273 and
-172 bp (threefold decrease when deleted), while activity in the
ejaculatory duct is conferred by more distal sequences between -844 and
-614 bp (fourfold decrease when deleted). The reproductive tract activity
is further modulated by two additional DNA regions, one in 5' DNA (-613 to
-284 bp; threefold decrease when deleted) and the other in 3' DNA (+1860 to
+2731 bp; threefold decrease when deleted) that probably overlaps the
adjacent esteraseP gene. Collating these data with previous studies
suggests that expression of EST6 in the ancestral sites is mainly regulated
by conserved proximal sequences while more variable distal sequences
regulate expression in the acquired ejaculatory duct site.
相似文献