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951.
Amperometry is a powerful voltammetric measuring method. Its application is specially advantageous when used in combination with a separation step or with some other sample treatment method providing selectivity. The selectivity is often achieved by coating the amperometric working electrode surface with a membrane of special character. Size exclusion membrane, immobilized enzyme containing reaction layer, protecting dialysis membrane, perm selective ion exchange film etc can be mentioned here. In conventional amperometry the measuring potential is continuously applied, therefore in case of membrane coated electrodes the electrode process depletes the diffusion layer. In this work the performance of a new periodically interrupted amperometric (PIA) measuring program has been investigated in case of glucose enzyme sensor. The measuring program allowing time for reloading the diffusion layer provided higher current and therefore improved sensitivity and lower limit of detection. 相似文献
952.
The aim of our study was to, in accordance with the presented theoretical presumptions, analyze the possible reasons for hip fractures of the older population in the north-eastern part of Croatia. A group of 2,696 persons (1,936 women and 760 men) with hip fractures has been analyzed during a 12 year period (from 1993. until 2005. year) in the Clinical Hospital Osijek. The date of admittance, age, gender and fracture location were recorded. In men, the incidence of total hip fracture number on the left side was greater 23.5% (p<0.01) compared to the right side, while in women this difference does not exist. Men have a greater incidence of trochanteric fractures than fractures of femoral neck on both sides, while in women this difference could be shown on the right side only. In women, a 30.5% (p<0.001) higher fracture incidence occurred in the winter compared to the summer. It has been concluded that in men the impaired neuromuscular function on the left body side caused the greater incidence of falls on this side. The more frequent multifragmental fractures of the trochanteric massive in men indicate the possible role of preserved pelvitrochanteric muscle tension in fracture characterization. Increased incidence of falls and fractures in the older female population can be interpreted with a more pronounced weakness of pelvitrochanteric muscles and consequent walking instability. Furthermore, a smaller incidence of hip fractures was noticed in the summer compared with winter. This is explained by a reduced exhaustion of pelvic muscles in summer (primarily pelvitrochanteric) and decrease in fall frequency. 相似文献
953.
954.
The superior colliculus (SC) in primates plays an important role in orienting gaze and arms toward novel stimuli. Here we ask whether neurons in the intermediate and deep layers of the SC are also involved in the interaction with objects. In two trained monkeys we found a large number of SC units that were specifically activated when the monkeys contacted and pushed a target that had been reached with either hand. These neurons, however, were silent when the monkeys simply looked at or reached for the target but did not touch it. The activity related to interacting with objects was spatially tuned and increased with push strength. Neurons in the SC with this type of activity may be involved in a somatosensory-motor feedback loop that monitors the force of the active muscles together with the spatial position of the limb required for proper interaction with an object. 相似文献
955.
P��ter Nagy Anthony J. Kettle Christine C. Winterbourn 《The Journal of biological chemistry》2009,284(22):14723-14733
The chemistry underlying superoxide toxicity is not fully understood. A
potential mechanism for superoxide-mediated injury involves addition to
tyrosyl radicals, to give peptide or protein hydroperoxides. The rate constant
for the reaction of tyrosyl radicals with superoxide is higher than for
dimerization, but the efficiency of superoxide addition to peptides depends on
the position of the Tyr residue. We have examined the requirements for
superoxide addition and structurally characterized the products for a range of
tyrosyl peptides exposed to a
peroxidase/
system. These included enkephalins as examples of the numerous proteins and
physiological peptides with N-terminal tyrosines. The importance of amino
groups in promoting hydroperoxide formation and effect of methionine residues
on the reaction were investigated. When tyrosine was N-terminal, the major
products were hydroperoxides that had undergone cyclization through conjugate
addition of the terminal amine. With non-N-terminal tyrosine, electron
transfer from
to the peptide radical prevailed. Peptides containing methionine revealed a
novel and efficient intramolecular oxygen transfer mechanism from an initial
tyrosine hydroperoxide to give a dioxygenated derivative with one oxygen on
the tyrosine and the other forming methionine sulfoxide. Exogenous amines
promoted hydroperoxide formation on tyrosyl peptides lacking a terminal amine,
without forming an adduct. These findings, plus the high hydroperoxide yields
with N-terminal tyrosine, can be explained by a mechanism in which hydrogen
bonding of
to the amine increases is oxidizing potential and alters its reactivity. If
this amine effect occurred more generally, it could increase the biological
reactivity of
and have major implications.Free radical-mediated oxidative damage occurs in numerous diseases and is
thought to contribute to the aging process. The primary radical generated by
the reduction of oxygen is superoxide
(),
a relatively benign radical that nevertheless must be removed by superoxide
dismutases (SODs)2 for
an organism to survive in an aerobic environment
(1). A number of potentially
damaging reactions of
have been identified
(1–4).
One of these, which has received relatively little attention, is the addition
of
to other radicals to form hydroperoxides
(5,
6). This reaction has been
shown to occur readily with tyrosine and Tyr-containing dipeptides, resulting
in the formation of tyrosine hydroperoxides
(5–7).
Hydroperoxides are potentially damaging reactive oxygen species. Formation on
proteins can result in detrimental structural and functional changes
(8). Protein hydroperoxides are
also oxidants that can injure other biomolecules.Tyrosyl radicals are generated in many physiological situations and
proteins are major targets for reactive oxidants
(9). In proteins exposed to
free radicals, regardless of the initial site of attack, the resultant radical
commonly localizes to Tyr
(10–13).
Tyrosyl radicals are also produced from tyrosyl peptides through the action of
peroxidases such as myeloperoxidase, and are generated during the catalytic
cycle of enzymes such as ribonucleotide reductase and cyclooxygenase
(14). Tyrosyl radicals undergo
a variety of subsequent reactions. They readily dimerize to form dityrosine,
which has been well documented as a product of oxidative injury
(15,
16). Another oxidative
biomarker, nitrotyrosine, is also formed via tyrosyl radicals
(4,
15,
17). However, one of their
most favored reactions is with
(5,
7,
18,
19). The reaction has a rate
constant several times higher than that for dimerization
(7,
20) and is favored over
dityrosine formation in situations where both tyrosyl and
radicals are generated (7,
20).The reaction of
with phenoxyl radicals results in either repair of the parent phenol (reaction
2, Fig. 1b) or
addition to form a hydroperoxide (reaction 3). With tyrosine, most of the
reacts by addition (7,
20). The structure of tyrosine
hydroperoxide has not been determined directly but inferred from NMR studies
of the corresponding monoxide derivative formed by slow decomposition
(7). These were shown to be
bicyclic compounds formed by conjugate addition of the amino group to the
phenol ring (HOHICA, designated I and named in full in
Fig. 1b, proposed to
arise from reactions 5 and 6).Open in a separate windowFIGURE 1.a, experimental system used for the generation of superoxide and
tyrosyl (TyrO·) radicals. b, proposed mechanism for
the formation and decomposition of tyrosine hydroperoxide derivatives.
R and R′ represent OH and H, respectively, for Tyr, or
amino acid residue(s) for the peptides. Reaction 1 shows
peroxidase-mediated formation of Tyr radicals, which can either dimerize (not
shown) or react with
by electron transfer (reaction 2) or addition (reaction 3).
Addition results in the formation of hydroperoxides (o- and
p-isomers, only the o-isomer shown) that may exist
transiently and decompose to release 1O2 (reaction 4) or
form a stable species that can undergo conjugate addition of the terminal
amino group are shown (when R′= H, reaction 5). An equivalent
reaction is proposed for non-N-terminal Tyr (R′= amino acid residue) in
which conjugation involves the amide nitrogen. Hydrolysis of the
hydroperoxides that are modified by conjugate addition gives the corresponding
hydroxide derivatives (I,
3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-indol-2-carboxylic acid or HOHICA)
in reaction 6. c, possible alternative hydrolysis products
(mono-oxygenated derivatives). II, 3,4-dihydroxyphenylalanine
derivatives from the o-isomer; III,
4-alanyl-4-hydroxy-cyclohexadienone (HACHD) derivatives from the
p-isomer.Hydroperoxide formation has been observed with peptides but only when
tyrosine is N-terminal or the reaction is promoted by amino compounds
(5). The amine effect has
implications for hydroperoxide formation on proteins, but the mechanism is not
understood. It has also been postulated that the repair mechanism involves
singlet oxygen release from an intermediate (reaction 4) rather than
electron transfer (reaction 2)
(18), but this has not been
studied experimentally.The objectives of this investigation were to determine the structures of
the hydroperoxide and any other superoxide addition products, and to
understand the mechanism of formation, using a range of synthetic and
physiological tyrosyl peptides. These include the opioids Leu- and
Met-Enkephalin (Leu-Enk, YGGFL; and Met-Enk, YGGFM, respectively) and
Endomorphin 2 (Endo2, YPFF). The opioids have a free N-terminal Tyr that is
essential for activity and are potential physiological targets for
inactivation by
addition. We also investigated whether the presence of a Met residue (as in
Met-Enk) influences Tyr-hydroperoxide formation on the peptide and whether
addition results in the formation of methionine sulfoxide. If so, this could
be a physiological mechanism for production of methionine sulfoxide, which is
one of the most prevalent products of oxidative stress
(21,
22).Peptides were exposed to a xanthine oxidase (XO) system to generate
and hydrogen peroxide (H2O2) plus horseradish peroxidase
(HRP) to catalyze the reaction of H2O2 with the peptide
to give the tyrosyl radical (Fig.
1a). Products were analyzed using a general hydroperoxide
assay (Fe2+/xylenol orange or FOX assay) and by liquid
chromatography/electrospray mass spectrometry (LC/MS). We have obtained
structural information on the hydroperoxides, identified a mechanism of rapid
intramolecular oxidation of Met residues via a hydroperoxide intermediate, and
provide an explanation for why amino groups facilitate the addition of
to the tyrosyl radical. 相似文献
956.
Vörös A Horváth B Hunyadkürti J McDowell A Barnard E Patrick S Nagy I 《Journal of bacteriology》2012,194(6):1621-1622
Propionibacterium acnes is an anaerobic Gram-positive bacterium that has been linked to a wide range of opportunistic human infections and conditions, most notably acne vulgaris (I. Kurokawa et al., Exp. Dermatol. 18:821-832, 2009). We now present the whole-genome sequences of three P. acnes strains from the type IA(2) cluster which were recovered from ophthalmic infections (A. McDowell et al., Microbiology 157:1990-2003, 2011). 相似文献
957.
Rienmüller F Dreyer I Schönknecht G Schulz A Schumacher K Nagy R Martinoia E Marten I Hedrich R 《The Journal of biological chemistry》2012,287(12):8986-8993
Proton pumping of the vacuolar-type H(+)-ATPase into the lumen of the central plant organelle generates a proton gradient of often 1-2 pH units or more. Although structural aspects of the V-type ATPase have been studied in great detail, the question of whether and how the proton pump action is controlled by the proton concentration on both sides of the membrane is not understood. Applying the patch clamp technique to isolated vacuoles from Arabidopsis mesophyll cells in the whole-vacuole mode, we studied the response of the V-ATPase to protons, voltage, and ATP. Current-voltage relationships at different luminal pH values indicated decreasing coupling ratios with acidification. A detailed study of ATP-dependent H(+)-pump currents at a variety of different pH conditions showed a complex regulation of V-ATPase activity by both cytosolic and vacuolar pH. At cytosolic pH 7.5, vacuolar pH changes had relative little effects. Yet, at cytosolic pH 5.5, a 100-fold increase in vacuolar proton concentration resulted in a 70-fold increase of the affinity for ATP binding on the cytosolic side. Changes in pH on either side of the membrane seem to be transferred by the V-ATPase to the other side. A mathematical model was developed that indicates a feedback of proton concentration on peak H(+) current amplitude (v(max)) and ATP consumption (K(m)) of the V-ATPase. It proposes that for efficient V-ATPase function dissociation of transported protons from the pump protein might become higher with increasing pH. This feature results in an optimization of H(+) pumping by the V-ATPase according to existing H(+) concentrations. 相似文献
958.
Alice Rokszin Zita Márkus Gábor Braunitzer Antal Berényi Marek Wypych Wioletta J. Waleszczyk György Benedek Attila Nagy 《Central European Journal of Biology》2010,5(1):21-30
Our study compares the spatio-temporal visual receptive field properties of different subcortical stages of the ascending
tectofugal visual system. Extracellular single-cell recordings were performed in the superficial (SCs) and intermediate (SCi)
layers of the superior colliculus (SC), the suprageniculate nucleus (Sg) of the posterior thalamus and the caudate nucleus
(CN) of halothane-anesthetized cats. Neuronal responses to drifting gratings of various spatial and temporal frequencies were
recorded. The neurons of each structure responded optimally to low spatial and high temporal frequencies and displayed narrow
spatial and temporal frequency tuning. The detailed statistical analysis revealed that according to its stimulus preferences
the SCs has markedly different spatio-temporal properties from the homogeneous group formed by the SCi, Sg and CN. The SCs
neurons preferred higher spatial and lower temporal frequencies and had broader spatial tuning than the other structures.
In contrast to the SCs the visually active SCi, as well as the Sg and the CN neurons possessed consequently similar spatio-temporal
preferences. These data support our hypothesis that the visually active SCi, Sg and CN neurons form a homogeneous neuronal
population given a similar spatio-temporal frequency preference and a common function in processing of dynamic visual information. 相似文献
959.
Xingsheng Li Mark B. Cope Maria S. Johnson Daniel L. Smith Jr Tim R. Nagy 《Obesity (Silver Spring, Md.)》2010,18(3):456-462
This study investigated the effects of mild calorie restriction (CR) (5%) on body weight, body composition, energy expenditure, feeding behavior, and locomotor activity in female C57BL/6J mice. Mice were subjected to a 5% reduction of food intake relative to baseline intake of ad libitum (AL) mice for 3 or 4 weeks. In experiment 1, body weight was monitored weekly and body composition (fat and lean mass) was determined at weeks 0, 2, and 4 by dual energy X‐ray absorptiometry. In experiment 2, body weight was measured every 3 days and body composition was determined by quantitative magnetic resonance weekly, and energy expenditure, feeding behavior, and locomotor activity were determined over 3 weeks in a metabolic chamber. At the end of both experiments, CR mice had greater fat mass (P < 0.01) and less lean mass (P < 0.01) compared with AL mice. Total energy expenditure (P < 0.05) and resting energy expenditure (P < 0.05) were significantly decreased in CR mice compared with AL mice over 3 weeks. CR mice ate significantly more food than AL mice immediately following daily food provisioning at 1600 hours (P < 0.01). These findings showed that mild CR caused increased fat mass, decreased lean mass and energy expenditure, and altered feeding behavior in female C57BL/6J mice. Locomotor activity or brown adipose tissue (BAT) thermogenic capacity did not appear to contribute to the decrease in energy expenditure. The increase in fat mass and decrease in lean mass may be a stress response to the uncertainty of food availability. 相似文献
960.
Judit M. Nagy 《Proteomics》2010,10(10):1903-1905
The Biological Reference Material Initiative Workshop held at the Toronto HUPO congress on 26 September 2009, focused on the development of new biological reference materials and tools for the assessment of reproducibility, the solutions to many of the technical challenges in proteomics and protein‐based molecular diagnostics. This half‐day meeting included presentations from leading scientists from the worldwide proteomic community, who shared a common interest in standardization and increased accuracy of proteomic data. The conclusion was that proteomics is highly sensitive to both biological and technical variability. It is this biological and technical variance, when not accounted for by experiment design, that invalidates proteomic experiments, but both of these issues can be dealt with by tackling reproducibility. 相似文献