全文获取类型
收费全文 | 2691篇 |
免费 | 129篇 |
国内免费 | 2篇 |
出版年
2023年 | 11篇 |
2022年 | 29篇 |
2021年 | 64篇 |
2020年 | 29篇 |
2019年 | 36篇 |
2018年 | 72篇 |
2017年 | 55篇 |
2016年 | 75篇 |
2015年 | 112篇 |
2014年 | 146篇 |
2013年 | 178篇 |
2012年 | 191篇 |
2011年 | 199篇 |
2010年 | 113篇 |
2009年 | 96篇 |
2008年 | 203篇 |
2007年 | 181篇 |
2006年 | 190篇 |
2005年 | 154篇 |
2004年 | 131篇 |
2003年 | 131篇 |
2002年 | 124篇 |
2001年 | 22篇 |
2000年 | 19篇 |
1999年 | 16篇 |
1998年 | 15篇 |
1997年 | 16篇 |
1996年 | 14篇 |
1995年 | 9篇 |
1994年 | 9篇 |
1993年 | 11篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1988年 | 9篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 7篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 8篇 |
1979年 | 9篇 |
1978年 | 11篇 |
1975年 | 12篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1972年 | 4篇 |
1970年 | 3篇 |
排序方式: 共有2822条查询结果,搜索用时 15 毫秒
231.
We present the codimensional principal component analysis (PCA), a novel and straightforward method for resolving sample heterogeneity within a set of cryo-EM 2D projection images of macromolecular assemblies. The method employs PCA of resampled 3D structures computed using subsets of 2D data obtained with a novel hypergeometric sampling scheme. PCA provides us with a small subset of dominating "eigenvolumes" of the system, whose reprojections are compared with experimental projection data to yield their factorial coordinates constructed in a common framework of the 3D space of the macromolecule. Codimensional PCA is unique in the dramatic reduction of dimensionality of the problem, which facilitates rapid determination of both the plausible number of conformers in the sample and their 3D structures. We applied the codimensional PCA to a complex data set of Thermus thermophilus 70S ribosome, and we identified four major conformational states and visualized high mobility of the stalk base region. 相似文献
232.
Extracellular DNA is abundant and important for microcolony strength in mixed microbial biofilms 总被引:1,自引:0,他引:1
A new approach for quantification of extracellular DNA (eDNA) in mixed biofilms at microscale resolution was developed and combined with other staining techniques to assess the origin, abundance and role of eDNA in activated sludge biofilms. Most eDNA was found in close proximity to living cells in microcolonies, suggesting that most of it originated from an active secretion or alternatively, by lysis of a sub-population of cells. When the staining was combined with fluorescence in situ hybridization for identification of the microorganisms, it was found that the eDNA content varied among the different probe-defined species. The highest amount of eDNA was found in and around the microcolonies of denitrifiers belonging to the genera Curvibacter and Thauera, the ammonium-oxidizing Nitrosomonas and the nitrite-oxidizing Nitrospira. Other floc-formers also produced eDNA, although in lower amounts. The total eDNA content in activated sludge varied from 4 to 52 mg per gram volatile suspended solids in different wastewater treatment plants. Very high local concentrations within some microcolonies were found with up to approximately 300 mg of eDNA per g of organic matter. DNase digestion of activated sludge led to general floc disintegration and disruption of the microcolonies with high eDNA content, implying that eDNA was an important structural component in activated sludge biofilms. 相似文献
233.
Kudryashev M Cyrklaff M Alex B Lemgruber L Baumeister W Wallich R Frischknecht F 《Cellular microbiology》2011,13(5):731-741
Some Borrelia species are the causative agents of tick-borne Lyme disease responsible for different disabilities depending on species and hosts. Borrelia are highly motile bacterial cells, and light microscopy shows that these spirochetes can associate with each other during movement. Using cryo-electron tomography, we observed closely associated Borrelia cells. Some of these showed a single outer membrane surrounding two longitudinally arranged cytoplasmic cylinders. We also observed fusion of two cytoplasmic cylinders and differences in the surface layer density of fused spirochetes. These processes could play a role in the interaction of Borrelia species with the host's immune system. 相似文献
234.
235.
Glucosamine-6-phosphate (GlcN-6-P) synthase catalyses the first and practically irreversible step in hexosamine metabolism.
The final product of this pathway, uridine 5’ diphospho N-acetyl-D-glucosamine (UDP-GlcNAc), is an essential substrate for
assembly of bacterial and fungal cell walls. Moreover, the enzyme is involved in phenomenon of hexosamine induced insulin
resistance in type II diabetes, which makes it a potential target for antifungal, antibacterial and antidiabetic therapy.
The crystal structure of the isomerase domain of GlcN-6-P synthase from human pathogenic fungus Candida albicans, in complex with UDP-GlcNAc has been solved recently but it has not revealed the molecular mechanism of inhibition taking
place under UDP-GlcNAc influence, the unique feature of the eukaryotic enzyme. UDP-GlcNAc is a physiological inhibitor of
GlcN-6-P synthase, binding about 1 nm away from the active site of the enzyme. In the present work, comparative molecular
dynamics simulations of the free and UDP-GlcNAc-bounded structures of GlcN-6-P synthase have been performed. The aim was to
complete static X-ray structural data and detect possible changes in the dynamics of the two structures. Results of the simulation
studies demonstrated higher mobility of the free structure when compared to the liganded one. Several amino acid residues
were identified, flexibility of which is strongly affected upon UDP-GlcNAc binding. Importantly, the most fixed residues are
those related to the inhibitor binding process and to the catalytic reaction. The obtained results constitute an important
step toward understanding of mechanism of GlcN-6-P synthase inhibition by UDP-GlcNAc molecule. 相似文献
236.
Halina Szatyłowicz Tadeusz Marek Krygowski Aneta Jezierska-Mazzarello 《Journal of molecular modeling》2011,17(1):125-131
Due to gradual and controlled changes of interatomic distances between heavy atoms in OH…F− of C6H5OH…F− systems it was possible to study the electronic structure evolution. Computation at B3LYP/6-311+G(d,p) level of theory was
performed for this purpose. Changes in charges at atoms and characteristics at bond critical points (BCPs) of the H-bond region
and also in distant parts of the systems were investigated by means of natural bond orbitals (NBO) and atoms in molecules
(AIM) analyses. It is shown that at the border line between partially covalent and non-covalent H-bonding (Espinosa et al.
in J Chem Phys 117:5529, 2002; Grabowski et al. in J Phys Chem B 110:6444, 2006) with the H…F interatomic distance ∼1.8 Ǻ the hydrogen atom has the most positive charge. In addition, the change in the
atomic charge values in the interacting region affects the phenyl ring properties. The decrease of the sum of atomic charges
as well as of the aromaticity was noticed when the OH….F distance is shortened. 相似文献
237.
Highkin MK Yates MP Nemirovskiy OV Lamarr WA Munie GE Rains JW Masferrer JL Nagiec MM 《Journal of biomolecular screening》2011,16(2):272-277
To facilitate discovery of compounds modulating sphingosine-1-phosphate (S1P) signaling, the authors used high-throughput mass spectrometry technology to measure S1P formation in human whole blood. Since blood contains endogenous sphingosine (SPH) and S1P, mass spectrometry was chosen to detect the conversion of an exogenously added 17-carbon-long variant of sphingosine, C17SPH, into C17S1P. The authors developed procedures to achieve homogeneous mixing of whole blood in 384-well plates and for a method requiring minimal manipulations to extract S1P from blood in 96- and 384-well plates prior to analyses using the RapidFire(?) mass spectrometry system. 相似文献
238.
239.
Błaszczyk L Popiel D Chełkowski J Koczyk G Samuels GJ Sobieralski K Siwulski M 《Journal of applied genetics》2011,52(2):233-243
In the present study, we reinvestigate the diversity of Trichoderma in Poland utilizing a combination of morphological and molecular/phylogenetic methods. A total of 170 isolates were collected
from six different substrata at 49 sites in Poland. These were divided among 14 taxa as follows: 110 of 170 Trichoderma isolates were identified to the species level by the analysis of their ITS1, ITS2 rDNA sequences as: T. harzianum (43 isolates), T. aggressivum (35), T. citrinoviride (11), T. hamatum (9), T. virens (6), T. longibrachiatum (4), T. polysporum (1), and T. tomentosum (1); 60 isolates belonging to the Viride clade were identified based on a fragment of the translation-elongation factor 1-alpha
(tef1) gene as: T. atroviride (20 isolates), T. gamsii (2), T. koningii (17), T. viridescens (13), T. viride (7), and T. koningiopsis (1). Identifications were made using the BLAST interface in TrichOKEY and TrichoBLAST (). The most diverse substrata were soil (nine species per 22 isolates) and decaying wood (nine species per 75 isolates). The
most abundant species (25%) isolated from all substrata was T. harzianum. 相似文献
240.
STIM1 is an endoplasmic reticulum (ER) membrane Ca(2+) sensor responsible for activation of store-operated Ca(2+) influx. We discovered that STIM1 oligomerization and store-operated Ca(2+) entry (SOC) are modulated by the ER oxidoreductase ERp57. ERp57 interacts with the ER luminal domain of STIM1, with this interaction involving two conserved cysteine residues, C(49) and C(56). SOC is accelerated in the absence of ERp57 and inhibited in C(49) and C(56) mutants of STIM1. We show that ERp57, by ER luminal interaction with STIM1, has a modulatory role in capacitative Ca(2+) entry. This is the first demonstration of a protein involved in ER intraluminal regulation of STIM1. 相似文献