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1.
Previous experience with the Langevin/implicit-Euler scheme for dynamics (“LI”) on model systems (butane, water) has shown that LI is numerically stable for timesteps in the 5–20 fs range but quenches high-frequency modes. To explore applications to polypeptides, we apply LI to model systems (several dipeptides, a tetrapeptide, and a 13-residue oligoalanine) and also develop a new dynamics driver approach (“DA”). The DA scheme, based on LI, addresses the important issue of proper sampling, which is unlikely to be solved by small-time step integration methods or implicit methods with intrinsic damping at room temperature, such as LI. Equilibrium averages, time-dependent molecular properties, and sampling trends at room temperature are reported for both LI and DA dynamics simulations, which are then compared to those generated by a standard explicit discretization of the Langevin equation with a 1 fs timestep. We find that LI's quenching effects are severe on both the fast and slow (due to vibrational coupling) frequency modes of all-atom polypeptides and lead to more restricted dynamics at moderate timesteps (40 fs). The DA approach empirically counteracts these damping effects by adding random atomic perturbations to the coordinates at each step (before the minimization of a dynamics function). By restricting the energetic fluctuations and controlling the kinetic energy, we are able with a 60 fs timestep to generate continuous trajectories that sample more of the relevant conformational space and also reproduce reasonably Boltzmann statistics. Although the timescale for transition may be accelerated by the DA approach, the transitional. information obtained for the alanine dipeptide and the tetrapeptide is consistent with that obtained by several other theoretical approaches that focus specifically on the determination of pathways. While the trajectory for oligoalanine by the explicit scheme over the nanosecond timeframe remains in the vicinity of the full αR-helix starting structure, and a high-temperature (6000°K) MD trajectory departs slowly from the a helical structure, the DA-generated trajectory for the same CPU time exhibits unfolding and refolding and reveals a range of conformations with an intermediate helix content. Significantly, this range of states is more consistent with spectroscopic experiments on small peptides, as well as the cooperative two-state model for helix–coil transition. The good, near-Boltzmann statistics reported for the smaller systems above, in combination with the interesting oligoalanine results, suggest that DA is a promising tool for efficiently exploring conformational spaces of biomolecules and exploring folding/unfolding processes of polypeptides. © 1995 Wiley-Liss, Inc. 相似文献
2.
Cheng Ly Tamar Melman Alison L. Barth G. Bard Ermentrout 《Journal of computational neuroscience》2011,30(2):211-223
BK channels are large conductance potassium channels gated by calcium and voltage. Paradoxically, blocking these channels has been shown experimentally to increase or decrease the firing rate of neurons, depending on the neural subtype and brain region. The mechanism for how this current can alter the firing rates of different neurons remains poorly understood. Using phase-resetting curve (PRC) theory, we determine when BK channels increase or decrease the firing rates in neural models. The addition of BK currents always decreases the firing rate when the PRC has only a positive region. When the PRC has a negative region (type II), BK currents can increase the firing rate. The influence of BK channels on firing rate in the presence of other conductances, such as I m and I h , as well as with different amplitudes of depolarizing input, were also investigated. These results provide a formal explanation for the apparently contradictory effects of BK channel antagonists on firing rates. 相似文献
3.
Musculo-skeletal allografts sterilized and deep frozen are among the most common human tissue to be preserved and utilized
in modern medicine. The effects of a long deep freezing period on cortical bone has already been evaluated and found to be
insignificant. However, there are no reports about the influences of a protracted deep freezing period on osteochondral allografts.
One hundred osteochondral cylinders were taken from a fresh specimen and humeral heads of 1 year, 2 years, 3 years and 4 year
old bones. Twenty chips from each period, with a minimum of 3 chips per humeral head. Each was mechanically tested by 3 point
compression. The fresh osteochondral allografts were significantly mechanically better than the deep frozen osteochondral
allografts. There was no statistical significant time dependent difference between the deep frozen groups in relation to the
freezing period. Therefore, we conclude that, from the mechanical point of view deep freezing of osteochondral allografts
over a period of 4 years, is safe without further deterioration of the biomechanical properties of the osteochondral allografts. 相似文献
4.
Changiz Geula Sara R. Dunlop Ivan Ayala Allegra S. Kawles Margaret E. Flanagan Tamar Gefen Marek-Marsel Mesulam 《Journal of neurochemistry》2021,158(6):1394-1411
5.
Nino Asatiani Tamar Kartvelishvili Marina Abuladze Lali Asanishvili Nelly Sapojnikova 《Biological trace element research》2011,142(3):388-397
The changes in glutathione-dependent cycle enzymes and catalase activities under Cr(VI)-induced oxidative stress were investigated
in two distinct cell lines: L-41−human epithelial-like cells and HLF−fetal human diploid lung fibroblasts, which differ in
tissue origin, proliferation, and antioxidant enzymes activities. The chromium concentrations from 1 to 5 μM cause nontoxic
effects and activate antioxidant enzymes to overcome oxidative stress. In spite of some differences in the endogenous antioxidant
activities, both cell lines reveal the same range of toxic concentrations (20–30 μM). The irreversible inhibition of glutathione-dependent
antioxidant enzymes develops under toxic concentrations and serves as a marker of toxicity. The endogenous antioxidant activity
influences time-dependent expression of Cr(VI) toxicity and the dynamics of antioxidant enzymes activity under nontoxic conditions.
The cell antioxidant defense system is an important marker of the cell adaptive capacity under nontoxic and toxic conditions. 相似文献
6.
Aziza Nassar Nicole Sookhan Marta Santisteban Sandra C Bryant Judy C Boughey Tamar Giorgadze Amy Degnim 《Diagnostic pathology》2010,5(1):1-10
Aims
As one of the five Lactate dehydrogenase (LDH) isoenzymes, LDH5 has the highest efficiency to catalyze pyruvate transformation to lactate. LDH5 overexpression in cancer cells induces an upregulated glycolytic metabolism and reduced dependence on the presence of oxygen. Here we analyzed LDH5 protein expression in a well characterized large cohort of primary lung cancers in correlation to clinico-pathological data and its possible impact on patient survival.Methods
Primary lung cancers (n = 269) and non neoplastic lung tissue (n = 35) were tested for LDH5 expression by immunohistochemistry using a polyclonal LDH5 antibody (ab53010). The results of LDH5 expression were correlated to clinico-pathological data as well as to patient's survival. In addition, the results of the previously tested Transketolase like 1 protein (TKTL1) expression were correlated to LDH5 expression.Results
89.5% (n = 238) of NSCLC revealed LDH5 expression whereas LDH5 expression was not detected in non neoplastic lung tissues (n = 34) (p < 0.0001). LDH5 overexpression was associated with histological type (adenocarcinoma = 57%, squamous cell carcinoma = 45%, large cell carcinoma = 46%, p = 0.006). No significant correlation could be detected with regard to TNM-stage, grading or survival. A two sided correlation between the expression of TKTL1 and LDH5 could be shown (p = 0.002) within the overall cohort as well as for each grading and pN group. A significant correlation between LDH5 and TKTL1 within each histologic tumortype could not be revealed.Conclusions
LDH5 is overexpressed in NSCLC and could hence serve as an additional marker for malignancy. Furthermore, LDH5 correlates positively with the prognostic marker TKTL1. Our results confirm a close link between the two metabolic enzymes and indicate an alteration in the glucose metabolism in the process of malignant transformation. 相似文献7.
Revaz Solomonia Nana Gogichaishvili Maia Nozadze Eka Lepsveridze David Dzneladze Tamar Kiguradze 《Cellular and molecular neurobiology》2013,33(1):119-127
Identification of compounds preventing the biochemical changes that underlie the epileptogenesis process is of great importance. We have previously shown that myo-Inositol (MI) daily treatment prevents certain biochemical changes that are triggered by kainic acid (KA)-induced status epilepticus (SE). The aim of the current work was to study the further influence of MI treatment on the biochemical changes of epileptogenesis and focus on changes in the hippocampus and neocortex of rats for the following GABA-A receptor subunits: α1, α4, γ2, and δ. After SE, one group of rats was treated with saline, while the second group was treated with MI. Control groups that were not treated by the convulsant received either saline or MI administration. 28–30 h after the experiment, a decrease in the amount of the α1 subunit was revealed in the hippocampus and MI had no significant influence on it. On the 28th day of the experiment, the amount of α1 was increased in both the KA? and KA + MI-treated groups. The α4 and γ2 subunits were strongly reduced in the hippocampus of KA-treated animals, but MI significantly halted this reduction. The effects of MI on α4 and γ2 subunit changes were significantly different between hippocampus and neocortex. On the twenty-eighth day after SE, a decrease in the amount of α1 was found in the neocortex, but MI treatment had no effect on it. The obtained results indicate that MI treatment interferes with some of the biochemical processes of epileptogenesis. 相似文献
8.
9.
Martinez RJ Wang Y Raimondo MA Coombs JM Barkay T Sobecky PA 《Applied and environmental microbiology》2006,72(5):3111-3118
Aerobic heterotrophs were isolated from subsurface soil samples obtained from the U.S. Department of Energy's (DOE) Field Research Center (FRC) located at Oak Ridge, Tenn. The FRC represents a unique, extreme environment consisting of highly acidic soils with co-occurring heavy metals, radionuclides, and high nitrate concentrations. Four hundred isolates obtained from contaminated soil were assayed for heavy metal resistance, and a smaller subset was assayed for tolerance to uranium. The vast majority of the isolates were gram-positive bacteria and belonged to the high-G+C- and low-G+C-content genera Arthrobacter and Bacillus, respectively. Genomic DNA from a randomly chosen subset of 50 Pb-resistant (Pb(r)) isolates was amplified with PCR primers specific for P(IB)-type ATPases (i.e., pbrA/cadA/zntA). A total of 10 pbrA/cadA/zntA loci exhibited evidence of acquisition by horizontal gene transfer. A remarkable dissemination of the horizontally acquired P(IB)-type ATPases was supported by unusual DNA base compositions and phylogenetic incongruence. Numerous Pb(r) P(IB)-type ATPase-positive FRC isolates belonging to the genus Arthrobacter tolerated toxic concentrations of soluble U(VI) (UO(2)(2+)) at pH 4. These unrelated, yet synergistic, physiological traits observed in Arthrobacter isolates residing in the contaminated FRC subsurface may contribute to the survival of the organisms in such an extreme environment. This study is, to the best of our knowledge, the first study to report broad horizontal transfer of P(IB)-type ATPases in contaminated subsurface soils and is among the first studies to report uranium tolerance of aerobic heterotrophs obtained from the acidic subsurface at the DOE FRC. 相似文献
10.
Autophagy is an evolutionary conserved process of bulk degradation and nutrient sequestration that occurs in all eukaryotic
cells. Yet, in recent years, autophagy has also been shown to play a role in the specific degradation of individual proteins
or protein aggregates as well as of damaged organelles. The process was initially discovered in yeast and has also been very
well studied in mammals and, to a lesser extent, in plants. In this review, we summarize what is known regarding the various
functions of autopahgy in plants but also attempt to address some specific issues concerning plant autophagy, such as the
insufficient knowledge regarding autophagy in various plant species other than Arabidopsis, the fact that some genes belonging to the core autophagy machinery in various organisms are still missing in plants, the
existence of autophagy multigene families in plants and the possible operation of selective autophagy in plants, a study that
is still in its infancy. In addition, we point to plant-specific autophagy processes, such as the participation of autophagy
during development and germination of the seed, a unique plant organ. Throughout this review, we demonstrate that the use
of innovative bioinformatic resources, together with recent biological discoveries (such as the ATG8-interacting motif), should
pave the way to a more comprehensive understanding of the multiple functions of plant autophagy. 相似文献