全文获取类型
收费全文 | 328篇 |
免费 | 34篇 |
国内免费 | 1篇 |
出版年
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 2篇 |
2018年 | 4篇 |
2017年 | 7篇 |
2016年 | 8篇 |
2015年 | 10篇 |
2014年 | 15篇 |
2013年 | 14篇 |
2012年 | 15篇 |
2011年 | 14篇 |
2010年 | 20篇 |
2009年 | 17篇 |
2008年 | 14篇 |
2007年 | 15篇 |
2006年 | 11篇 |
2005年 | 10篇 |
2004年 | 15篇 |
2003年 | 15篇 |
2002年 | 7篇 |
2001年 | 10篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 13篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1973年 | 7篇 |
1972年 | 6篇 |
1969年 | 3篇 |
1968年 | 4篇 |
1967年 | 2篇 |
1965年 | 4篇 |
排序方式: 共有363条查询结果,搜索用时 31 毫秒
1.
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
2.
Litman GW; Rast JP; Shamblott MJ; Haire RN; Hulst M; Roess W; Litman RT; Hinds- Frey KR; Zilch A; Amemiya CT 《Molecular biology and evolution》1993,10(1):60-72
Immunoglobulins are encoded by a large multigene system that undergoes
somatic rearrangement and additional genetic change during the development
of immunoglobulin-producing cells. Inducible antibody and antibody-like
responses are found in all vertebrates. However, immunoglobulin possessing
disulfide-bonded heavy and light chains and domain-type organization has
been described only in representatives of the jawed vertebrates. High
degrees of nucleotide and predicted amino acid sequence identity are
evident when the segmental elements that constitute the immunoglobulin gene
loci in phylogenetically divergent vertebrates are compared. However, the
organization of gene loci and the manner in which the independent elements
recombine (and diversify) vary markedly among different taxa. One striking
pattern of gene organization is the "cluster type" that appears to be
restricted to the chondrichthyes (cartilaginous fishes) and limits
segmental rearrangement to closely linked elements. This type of gene
organization is associated with both heavy- and light-chain gene loci. In
some cases, the clusters are "joined" or "partially joined" in the germ
line, in effect predetermining or partially predetermining, respectively,
the encoded specificities (the assumption being that these are expressed)
of the individual loci. By relating the sequences of transcribed gene
products to their respective germ-line genes, it is evident that, in some
cases, joined-type genes are expressed. This raises a question about the
existence and/or nature of allelic exclusion in these species. The
extensive variation in gene organization found throughout the vertebrate
species may relate directly to the role of intersegmental
(V<==>D<==>J) distances in the commitment of the individual
antibody-producing cell to a particular genetic specificity. Thus, the
evolution of this locus, perhaps more so than that of others, may reflect
the interrelationships between genetic organization and function.
相似文献
3.
Jan Oscarsson Yoshimitsu Mizunoe Bernt Eric Uhlin David J. Haydon 《Molecular microbiology》1996,20(1):191-199
The Salmonella typhimurium protein SlyAST, originally described as a cytolysin, shows sequence similarities to several known bacterial regulatory proteins. A homologue to the slyASt gene has been localised to min 37 of the Eschericia coli K-12 chromosome and has been designated slyAEC When introduced in trans on a plasmid, the slyAEC gene conferred a haemolytic phenotype on wild-type but not clyA-knockout strains of E. coli K-12. The clyA gene encodes a novel haemolysin that is not expressed by wild-type E. coli under tested laboratory conditions. Western and Northern blot analyses, and DNA-band-shift assays support a model whereby the SlyAEC protein activates clyA expression by binding to the clyA promoter region, thereby supporting the sequence similarity data in suggesting that SlyAST is a haemolysin activator rather than being a haemolysin per se. 相似文献
4.
The 1000-1300 cm-1 region of the infrared spectrum of dipalmitoylphosphatidylcholine (DPPC) and other phosphate-containing molecules has been studied by the Fourier-transform technique. Three absorption bands have been assigned to various vibrational modes of the DPPC phosphate group, with maximum wavenumbers at 1060, 1086 and 1222 cm-1. These values are the same above and below Tc of the phospholipid. Dehydration produces band-shifts toward higher wavenumbers . 相似文献
5.
J E Aswell A H Haydon H R Turner C A Dawkins J E Arceneaux 《Journal of bacteriology》1977,130(1):173-180
Membrane vesicles of Bacillus megaterium strains SK11 and Ard1 bound the ferrischizokinen and ferriferrioxamine B siderhores (iron transport cofactors). An approximately equimolar uptake of both labels of [3H, 59Fe]ferrischizokinen indicated binding of the intact chelate. Binding reached equilibrium in 2 to 5 min, was temperature independent, and was unaltered by the addition of several energy sources. A 91% dissociation of bound [Fe]ferrischizokinen was achieved in 60 s by the addition of excess ferrischizokinen. Ferriaerobactin, a siderophore which is structurally related to ferrischizokinen, caused no detectable release of bound [59Fe]ferrischizokinen. Of several other ferrigydroxamates tested, only ferriferrichrome A achieved the release (11%) of [Fe]ferrischizokinen. Rapid dissociation (92%) of bound [59Fe]ferriferrioxamine B by the addition of ferriferrioxamine B was observed, and a 67% release of [59Fe]ferriferrioxamine B was caused by ferriA2265, its structural relative. Ferrischizokinen, ferriferrichrome A, and ferrirhodotorulic acid produced a 6, 25, and 29% dissociation, respectively, of [59Fe]ferriferrioxamine B; ferriaerobactin caused no dissociation. [59Fe]ferriaerobactin was bound by the membranes, but its dissociation was not effected by unlabeled ferriaerobactin, suggesting no specific receptors for this chelate. The respective binding affinity constants and maximal binding capacities of membrane vesicles of strain SK11 were 2 x 10(7) M-1 and 280 pmol per mg of protein for ferrischizokinen and 7 x 10(7) M-1 and 37 pmol per mg of protein for ferriferrioxamine B. These values in strain Ard1 were, respectively, 1.4 x 10(7) M-1 and 186 pmol per mg of protein for ferrischizokinen and 11 x 10(7) M-1 and 23 pmol per mg of protein for ferriferrioxamine B. Separate, specific binding sites (receptors) for ferrischizokinen and ferriferrioxamine B exist on the vesicles. The ferrischizokinen receptors have a lower affinity but a higher binding capacity (eightfold) than that shown by the ferriferrioxamine B receptor. These receptors may be components of independent transport systems. 相似文献
6.
7.
8.
A mean-field model of the alkane-saturated lipid bilayer above its phase transition. II. Results and comparison with experiment.
下载免费PDF全文
![点击此处可从《Biophysical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Equilibrium properties of a model lipid bilayer saturated with an n-alkane are presented. The model exhibits a cut-off in absorption as the chain length of the alkane increases which is similar to that observed with black lipid films. The reasons for this cut-off are explored in detail. The model provides qualitative agreement with the experimental enthalpies of transfer of the various alkanes from bulk pure liquid to the bilayer, and with results of electrical compression experiments on black films. Distributions of alkane across the bilayer for different volume fractions in the membrane are presented. For small volume fractions of alkane, its distribution is fairly even across the bilayer and the alkane chains line up essentially parallel to the lipid chains. For larger volume fractions, the alkane distribution is strongly peaked in the center of the membrane. The alkane chains in the outer regions of the membrane line up essentially parallel to the lipid chains, while those in the center are almost completely disordered. The model suggests that the chains (both lipid and alkane) are in an essentially liquid state with no well defined interface between opposing monolayers. It gives a possible explanation for the discrepancy between the experimental free energy of thinning of some lipid membranes formed from the longer chain length alkanes and the theoretical values estimated from Lifshitz's theory. 相似文献
9.
Robert Mason Helen C. Dearden Bella Nguyen Jennifer A. Soon Jessica Louise Smith Manreet Randhawa Andrew Mant Lydai Warburton Serigne Lo Tarek Meniawy Alexander Guminski Phillip Parente Sayed Ali Andrew Haydon Georgina V. Long Matteo S. Carlino Michael Millward Victoria G. Atkinson Alexander M. Menzies 《Pigment cell & melanoma research》2020,33(2):358-365
The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine‐protein kinase B‐Raf (BRAF)‐targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment‐naïve and 22% failed first‐line BRAF/MEK inhibitors. Treatment‐related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment‐naïve and 21% in BRAF/MEK failure patients. Median progression‐free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0‐NR) in treatment‐naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real‐world population. While first‐line efficacy appears comparable to trial populations, BRAF‐mutant patients failing prior BRAF/MEK inhibitors show less response. 相似文献
10.
Kenneth J. Ferguson Sarah Cleaveland Daniel Thomas Haydon Alexandre Caron Richard A. Kock Tiziana Lembo J. Grant C. Hopcraft Bertrand Chardonnet Thomas Nyariki Julius Keyyu David James Paton Fredrick Mathias Kivaria 《EcoHealth》2013,10(3):314-322
Strategies to control transboundary diseases have in the past generated unintended negative consequences for both the environment and local human populations. Integrating perspectives from across disciplines, including livestock, veterinary and conservation sectors, is necessary for identifying disease control strategies that optimise environmental goods and services at the wildlife-livestock interface. Prompted by the recent development of a global strategy for the control and elimination of foot-and-mouth disease (FMD), this paper seeks insight into the consequences of, and rational options for potential FMD control measures in relation to environmental, conservation and human poverty considerations in Africa. We suggest a more environmentally nuanced process of FMD control that safe-guards the integrity of wild populations and the ecosystem dynamics on which human livelihoods depend while simultaneously improving socio-economic conditions of rural people. In particular, we outline five major issues that need to be considered: 1) improved understanding of the different FMD viral strains and how they circulate between domestic and wildlife populations; 2) an appreciation for the economic value of wildlife for many African countries whose presence might preclude the country from ever achieving an FMD-free status; 3) exploring ways in which livestock production can be improved without compromising wildlife such as implementing commodity-based trading schemes; 4) introducing a participatory approach involving local farmers and the national veterinary services in the control of FMD; and 5) finally the possibility that transfrontier conservation might offer new hope of integrating decision-making at the wildlife-livestock interface. 相似文献