全文获取类型
收费全文 | 1599篇 |
免费 | 181篇 |
出版年
2023年 | 11篇 |
2022年 | 11篇 |
2021年 | 34篇 |
2020年 | 23篇 |
2019年 | 23篇 |
2018年 | 29篇 |
2017年 | 32篇 |
2016年 | 61篇 |
2015年 | 97篇 |
2014年 | 114篇 |
2013年 | 111篇 |
2012年 | 146篇 |
2011年 | 115篇 |
2010年 | 81篇 |
2009年 | 61篇 |
2008年 | 99篇 |
2007年 | 99篇 |
2006年 | 82篇 |
2005年 | 69篇 |
2004年 | 69篇 |
2003年 | 47篇 |
2002年 | 67篇 |
2001年 | 24篇 |
2000年 | 10篇 |
1999年 | 21篇 |
1998年 | 14篇 |
1997年 | 19篇 |
1996年 | 16篇 |
1995年 | 21篇 |
1994年 | 20篇 |
1993年 | 16篇 |
1992年 | 21篇 |
1991年 | 14篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 18篇 |
1987年 | 5篇 |
1985年 | 10篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
排序方式: 共有1780条查询结果,搜索用时 687 毫秒
141.
First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure 下载免费PDF全文
Jaspers NG Raams A Silengo MC Wijgers N Niedernhofer LJ Robinson AR Giglia-Mari G Hoogstraten D Kleijer WJ Hoeijmakers JH Vermeulen W 《American journal of human genetics》2007,80(3):457-466
Nucleotide excision repair (NER) is a genome caretaker mechanism responsible for removing helix-distorting DNA lesions, most notably ultraviolet photodimers. Inherited defects in NER result in profound photosensitivity and the cancer-prone syndrome xeroderma pigmentosum (XP) or two progeroid syndromes: Cockayne and trichothiodystrophy syndromes. The heterodimer ERCC1-XPF is one of two endonucleases required for NER. Mutations in XPF are associated with mild XP and rarely with progeria. Mutations in ERCC1 have not been reported. Here, we describe the first case of human inherited ERCC1 deficiency. Patient cells showed moderate hypersensitivity to ultraviolet rays and mitomycin C, yet the clinical features were very severe and, unexpectedly, were compatible with a diagnosis of cerebro-oculo-facio-skeletal syndrome. This discovery represents a novel complementation group of patients with defective NER. Further, the clinical severity, coupled with a relatively mild repair defect, suggests novel functions for ERCC1. 相似文献
142.
143.
Localization of metabotropic glutamate receptors in the outer plexiform layer of the goldfish retina
We studied the localization of metabotropic glutamate receptors (mGluRs) in the goldfish outer plexiform layer by light-and
electron-microscopical immunohistochemistry. The mGluR1α antibody labeled putative ON-type bipolar cell dendrites and horizontal
cell processes in both rod spherules and cone triads. Immunolabeling for mGluR2/3 was absent in the rod synaptic complex but
was found at horizontal cell dendrites directly opposing the cone synaptic ribbon. The mGluR5 antibody labeled Müller cell
processes wrapping rod terminals and horizontal cell somata. The mGluR7 antibody labeled mainly horizontal cell dendrites
invaginating rods and cones and some putative bipolar cell dendrites in the cone synaptic complex. The finding of abundant
expression of various mGluRs in bipolar and horizontal cell dendrites suggests multiple sites of glutamatergic modulation
in the outer retina.
Financial support for this work was provided by Conselho Nacional de Pesquisa (CNPq), Brazil (grant 200915/98-3 to C.J.) 相似文献
144.
External phosphorus load to a wetland with two shallow lakes in the Botshol Nature Reserve, The Netherlands, was reduced,
resulting in a rapid reduction of phytoplankton biomass and turbidity, and after 4 years, explosive growth of Characeae. The
clear water state was unstable, however, and the ecosystem then alternated between clear, high-vegetation and turbid, low-vegetation
states. A model of water quality processes was used in conjunction with a 14-year nutrient budget for Botshol to determine
if fluctuations in precipitation and nutrient load caused the ecosystem instability. The results indicate that, during wet
winters when groundwater level rose above surface water level, phosphorus from runoff was stored in the lake bottom and banks.
Stored phosphorus was released the following spring and summer under anaerobic sediment conditions, resulting in increased
phytoplankton density and light attenuation in the water column. During years with high net precipitation, flow from land
to surface water also transported humic acids, further increasing light attenuation. In years with dry winters, the phosphorus
and humic acid loads to surface water were reduced, and growth of submerged macrophytes was enhanced by clear water. Thus,
the temporal pattern of precipitation and flow from land to water gave a coherent, quantitative explanation of the observed
dynamics in phosphorus, phytoplankton, turbidity, and Characeae. Global warming has caused winters in The Netherlands to become
warmer and wetter during the last 50 years, increasing flow from land to water of humic acids and phosphorus and, ultimately,
enhancing instability of Characeae populations. In the first half of the 20th century interannual variation in precipitation
was not sufficient to cause large changes in internal P flux in Botshol, and submerged macrophyte populations were stable. 相似文献
145.
Flagellar motility and structure in the hyperthermoacidophilic archaeon Sulfolobus solfataricus 下载免费PDF全文
Szabó Z Sani M Groeneveld M Zolghadr B Schelert J Albers SV Blum P Boekema EJ Driessen AJ 《Journal of bacteriology》2007,189(11):4305-4309
Flagellation in archaea is widespread and is involved in swimming motility. Here, we demonstrate that the structural flagellin gene from the crenarchaeaon Sulfolobus solfataricus is highly expressed in stationary-phase-grown cells and under unfavorable nutritional conditions. A mutant in a flagellar auxiliary gene, flaJ, was found to be nonmotile. Electron microscopic imaging of the flagellum indicates that the filaments are composed of right-handed helices. 相似文献
146.
According to the equilibrium point theory, the control of posture and movement involves the setting of equilibrium joint positions
(EP) and the independent modulation of stiffness. One model of EP control, the α-model, posits that stable EPs and stiffness
are set open-loop, i.e. without the aid of feedback. The purpose of the present study was to explore for the elbow joint the
range over which stable EPs can be set open-loop and to investigate the effect of co-contraction on intrinsic low-frequency
elbow joint stiffness (K
ilf). For this purpose, a model of the upper and lower arm was constructed, equipped with Hill-type muscles. At a constant neural
input, the isometric force of the contractile element of the muscles depended on both the myofilamentary overlap and the effect
of sarcomere length on the sensitivity of myofilaments to [Ca2+] (LDCS). The musculoskeletal model, for which the parameters were chosen carefully on the basis of physiological literature,
captured the salient isometric properties of the muscles spanning the elbow joint. It was found that stable open-loop EPs
could be achieved over the whole range of motion of the elbow joint and that K
ilf, which ranged from 18 to 42 N m·rad−1, could be independently controlled. In the model, LDCS contributed substantially to K
ilf (up to 25 N m·rad−1) and caused K
ilf to peak at a sub-maximal level of co-contraction. 相似文献
147.
The relatively poor correlation between the risk of atherosclerotic plaque rupture and the degree of luminal obstruction before this event implies a strong imperative for in vivo detection of the processes underlying progressive plaque destabilization. In addition to the morphologic characteristics, apoptosis and inflammation comprise two important indicators of plaque instability. Apoptotic macrophage death results in enlargement of the plaque necrotic core and positive vascular remodelling, whereas apoptosis of the smooth muscle cells leads to attenuation of the fibrous cap. Imaging of apoptotic cells with annexin A5 provides an opportunity for the non-invasive assessment of cell death, and hence plaque vulnerability. The clinical detection of apoptosis could therefore promote the development of novel intervention strategies. 相似文献
148.
Folate fortification of rice by metabolic engineering 总被引:8,自引:0,他引:8
Storozhenko S De Brouwer V Volckaert M Navarrete O Blancquaert D Zhang GF Lambert W Van Der Straeten D 《Nature biotechnology》2007,25(11):1277-1279
Rice, the world's major staple crop, is a poor source of essential micronutrients, including folates (vitamin B9). We report folate biofortification of rice seeds achieved by overexpressing two Arabidopsis thaliana genes of the pterin and para-aminobenzoate branches of the folate biosynthetic pathway from a single locus. We obtained a maximal enhancement as high as 100 times above wild type, with 100 g of polished raw grains containing up to four times the adult daily folate requirement. 相似文献
149.
Reulen SW Brusselaars WW Langereis S Mulder WJ Breurken M Merkx M 《Bioconjugate chemistry》2007,18(2):590-596
Liposomes have become popular drug delivery vehicles and have more recently also been applied as contrast agents for molecular imaging. Most current methods for functionalization of liposomes with targeting proteins rely on reactions of amine or thiol groups at the protein exterior, which generally result in nonspecific conjugation at multiple sites on the protein. In this study, we present native chemical ligation (NCL) as a general method to covalently couple recombinant proteins in a highly specific and chemoselective way to liposomes containing cysteine-functionalized phospholipids. A cysteine-functionalized phospholipid (Cys-PEG-DSPE) was prepared and shown to readily react with the MESNA thioester of EYFP, which was used as a model protein. Characterization of the EYFP-liposomes using fluorescence spectroscopy showed full retention of the fluorescent properties of conjugated EYFP and provides a lower limit of 120 proteins per liposome. The general applicability of NCL was further tested using CNA35, a collagen-binding protein recently applied in fluorescent imaging of collagen. NCL of CNA35 thioester yielded liposomes containing approximately 100 copies of CNA35 per liposome. The CNA35-liposomes were shown to be fully functional and bind collagen with a 150-fold higher affinity compared to CNA35. Our results show that NCL is an attractive addition to existing conjugation methods that allows direct, covalent, and highly specific coupling of recombinant proteins to liposomes and other lipid-based assemblies. 相似文献
150.
Successful biological control of mist flower (Ageratina riparia) in New Zealand: Agent establishment, impact and benefits to the native flora 总被引:1,自引:0,他引:1
Jane Barton Simon V. Fowler Alison F. Gianotti Chris J. Winks Maarten de Beurs Greg C. Arnold Guy Forrester 《Biological Control》2007,40(3):370-385
The white smut fungus (Entyloma ageratinae) and the gall fly (Procecidochares alani) were released in New Zealand in 1998 and 2001 respectively to suppress mist flower (Ageratina riparia). The fungus established and spread rapidly, crossing 80 km of sea to Great Barrier Island within 2 years. The mean number of P. alani galls increased exponentially to 1.96/stem at release sites, but dispersal was slow. The impact of the biocontrol agents was monitored once annually from 1998/99 to 2003/04, at up to 51 sites in the North Island. The mean percentage of live leaves infected with fungus rapidly reached nearly 60%. Maximum plant height declined significantly. In heavy infestations, mean percentage cover of mist flower declined from 81 to 1.5%. Galls were only recorded towards the end of the impact study, and at low mean numbers. As mist flower declined, the species richness and mean percentage cover of native plants increased. In contrast, the species richness and mean percentage cover of exotic plants (excluding mist flower) did not change significantly. Many plant species colonizing the plots were important native mid- or late-successional shrubs or trees. With few exceptions, the exotic plant species common in the plots were not weeds that appeared to threaten native forest habitats. There was only a weak “replacement weed effect” from the potentially serious invader African club moss (Selaginella kraussiana). These data, together with reports of reduced threats to rare endemic plants from mist flower, suggest this rapid, well-monitored weed biocontrol program was very successful. 相似文献