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11.
《Cell》2022,185(20):3753-3769.e18
12.
Metals such as Cu2+, Fe3+, and Zn2+ are major contributors to the biology of a brain in stages of health, aging, and disease because of their unique effects on both protein structures (misfolding) and oxidative stress. The relationship between metal ions and neurodegenerative diseases is very complicated. Our study highlights how metal ions influence amyloid formation at low pH and on preformed amyloid fibrils. By using thioflavin T assay, ANS fluorescence, Congo red assay, circular dichroism, and microscopy to elucidate the effects of Cu2+, Fe3+, and Zn2+ on goat brain cystatin (GBC) aggregation at low pH. Results showed that Cu2+ and Fe3+ inhibit fibril formation of GBC by promoting amorphous aggregates. However, Zn2+ exclusively promotes fibril formation at low pH, leading to the formation of more ordered aggregates. Furthermore, the combined results of these complementary methods also suggested that Cu2+ and Fe3+ destabilize the β-sheet secondary structure of preformed amyloid fibrils of GBC. 相似文献
13.
5-Hydroxytryptamine (5-HT; 3 x 10(-8)-1 x 10(-5)M) produced a dose-dependent increase in phosphatidylinositol/polyphosphoinositide (PI) turnover in mouse cortical slices, as measured by following production of 3H-labelled inositol phosphates (IPs) in the presence of 10 mM LiCl. Analysis of individual IPs, in slices stimulated for 45 min, indicated substantial increases in inositol monophosphate (IP1; 140%) and inositol bisphosphate (IP2; 95%) contents with smaller increases in inositol trisphosphate (IP3; 51%) and inositol tetrakisphosphate (IP4; 48%) contents. The increase in IP3 level was solely in the 1,3,4-isomer. This response was inhibited by the nonselective 5-HT antagonists methysergide, metergoline, and spiperone. It was also inhibited by the selective 5-HT2 antagonists ketanserin and ritanserin but not by the 5-HT1 antagonists isapirone, (-)-propranolol, or pindolol. 5-HT-stimulated IP formation was also unaltered by atropine, prazosin, and mepyramine. Lesioning brain 5-HT neurones using 5,7-dihydroxytryptamine (5,7-DHT; 50 micrograms i.c.v.) produced a 210% (p less than 0.01) increase in the number of 5-HT2-mediated head-twitches induced by 5-methoxy-N,N-dimethyltryptamine (2 mg/kg). However, 5,7-DHT lesioning had no effect on 5-HT-stimulated PI turnover in these mice. Similarly, an electroconvulsive shock (90 V, 1 s) given five times over a 10-day period caused an 85% (p less than 0.01) increase in head-twitch responses but no change in 5-HT-stimulated PI turnover. Decreasing 5-HT2 function by twice-a-day injection of 5 mg/kg of zimeldine or desipramine (DMI) produced 50% (p less than 0.01) and 56% (p less than 0.01), respectively, reductions in head-twitch behaviour.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
14.
Glenn C. Conroy 《International journal of primatology》1987,8(2):115-137
Body-weight estimates of fossil primates are commonly used to infer many important aspects of primate paleobiology, including
diet, ecology, and relative encephalization. It is important to examine carefully the methodologies and problems associated
with such estimates and the degree to which one can have confidence in them. New regression equations for predicting body
weight in fossil primates are given which provide body-weight estimates for most nonhominid primate species in the fossil
record. The consequences of using different subgroups (evolutionary “grades”) of primate species to estimate fossil-primate
body weights are explored and the implications of these results for interpreting the primate fossil record are discussed.
All species (fossil and extant) were separated into the following “grades”: prosimian grade, monkey grade, ape grade, anthropoid
grade, and all-primates grade. Regression equations relating lower molar size to body weight for each of these grades were
then calculated. In addition, a female-anthropoid grade regression was also calculated for predicting body weight infernales
of extinct, sexually dimorphic anthropoid species. These equations were then used to generate the fossil-primate body weights.
In many instances, the predicted fossil-primate body weights differ substantially from previous estimates. 相似文献
15.
Brian T. Shea 《International journal of primatology》1987,8(2):139-156
In order to understand fully the generally high level of encephalization observed in living primates, we must determine why
early primates exhibited moderately large relative brain sizes compared to their early Tertiary contemporaries. The relatively
high degree of encephalization in early primates may be related at least in part to the fact that they were highly unusualamong mammals in combining a small body size with a strongly precocial reporductive strategy. Other small, precocial mammals
also exhibit moderately high levels of encephalization; but primates appear to have been truly uniquein being the only such small-sized and highly precocial group to give rise to extensive radiations of larger descendants.
This is a key element in understanding primate brain evolution, because the initial “head start” of the early primates was
translated up to larger sizes in descendants. The possible relationships among encephalization, precociality, small size,
and arboreality are discussed, particularly in light of recent debates concerning the validity of the superorder Archonta.
This work emphasizes that we need to consider relative brain size as but one element in a complex synergistic network of morphological
and life-history features. 相似文献
16.
A particle-induced X-ray emission (PIXE) analysis method is presented, which allows measurement of eight elements (i.e., K,
Ca, Mn, Fe, Cu, Zn, Se, and Rb) in human brain samples of only a few mg dry weight. The precision and accuracy of the method
were investigated by analyzing animal brain matter with both PIXE and instrumental neutron activation analysis (INAA). The
method was applied to measure the 8 elements in 46 different regions of 3 human brains. The sections analyzed originated from
either the left or the right cerebral hemisphere, brain stem, and cerebellum. For one of the brains, sections were also analyzed
from 26 corresponding regions of both hemispheres. For all elements, similar concentrations were found in the corresponding
areas of the left and right sides of the brain. The concentrations (in μg/g dry weight) of the elements K, Fe, Cu, Zn, Se,
and Rb were consistently higher in cortical structures than in white matter. Deep nuclei and brain stem, which have a mixed
composition, showed intermediate values for K, Zn, Se, and Rb. A hierarchical cluster analysis indicated that the various
brain regions clustered into two large groups, one comprising gray and mixed matter regions and the other, white and mixed
matter brain areas. 相似文献
17.
d-Aspartate in Human Brain 总被引:3,自引:3,他引:0
Eugene H. Man George H. Fisher Iris L. Payan Rodolfo Cadilla-Perezrios Nancy M. Garcia Radhika Chemburkar Georgine Arends William H. Frey II 《Journal of neurochemistry》1987,48(2):510-515
The presence of the biologically uncommon D-aspartic acid (D-aspartate) in human brain white matter has been previously reported. The earlier study has now been expanded to include D/L-aspartate ratios from 67 normal brains. The data show that the D-aspartate content increases rapidly from 1 year to approximately 35 years of age, levels off in middle age, and then appears to decrease somewhat. The D-aspartate content in gray matter remains at a consistently low level (half of that found in white matter) throughout the human life span. Within the limitations of current analytical methods, there was no detectable difference in D/L-aspartate ratios in white and gray matter of brains with Alzheimer's disease and several other pathologies when compared with brains of normal subjects. However, the presence of a significant D-aspartate level in white matter during the adult life span may lead to changes in protein configuration related to dysfunctions associated with the aging brain. 相似文献
18.
Cultures of dissociated brain cells from 15-day-old fetal mice were grown in the presence and absence of 20 or 50 nM triiodothyronine (T3), 30 or 300 nM cortisol, and 30 nM cortisol plus 50 nM T3 added to chemically defined media or in media supplemented with 15% serum from control and hypothyroid calves. The specific activities of five lysosomal enzymes--N-acetyl galactosaminidase, beta-glucuronidase, beta-galactosidase, cathepsin B, and dipeptidyl aminopeptidase I (DAP-I)--were higher in cells grown in calf serum than in cells grown in defined media. Of these enzymes, only DAP-I was elevated in activity when the cells were grown in hypothyroid calf serum instead of control calf serum. Elevation of DAP-I activity was reversed by addition of 20 nM T3 to hypothyroid calf serum. The enzymatic properties of DAP-I were similar whether the cells were grown in control or hypothyroid calf serum and were similar to those reported for human fibroblasts and the purified enzyme. When the cells were grown in defined media, cortisol decreased the activities of all lysosomal enzymes, with 300 nM cortisol being more effective than 30 nM cortisol. Addition of 50 nM T3 to 30 nM cortisol decreased DAP-I activity more than 30 nM cortisol alone, but 50 nM T3 alone in defined media did not alter DAP-I levels. The reduction of DAP-I activity in these cells by T3 required cortisol, unidentified components in serum, or both.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
19.
Hirotaka Yamamoto Hidehiko Konno Teiji Yamamoto Kitae Ito Michinao Mizugaki Yuzo Iwasaki 《Journal of neurochemistry》1987,49(2):603-609
Glutamine synthetase (GS) isolated from human brain formed a single band on sodium dodecyl sulfate-polyacrylamide gel with a molecular weight of 44,000. The enzyme had a specific activity of 179.2 U/mg protein when assayed by measuring the rate of the formation of gamma-glutamylhydroxamate using hydroxylamine as a substrate. In the presence of manganese ions, the relative activity of human brain GS was much lower than that of the sheep brain enzyme. The suppression of activity by increasing the ADP concentration, however, was less marked in the human enzyme than that in the sheep enzyme. Antibodies were raised in rabbits against the purified enzyme. The double-immunodiffusion technique disclosed cross-reactivities among GSs isolated from human, sheep, and rat brains, but the enzymes were not immunologically identical. Immunohistochemically, GS was localized in the cytoplasm of astrocytes in the human and rat brains and in pericentral hepatocytes of the liver. 相似文献
20.
O. Carter Snead III 《Journal of neurochemistry》1987,48(1):196-201
The presence of gamma-hydroxybutyric acid (GHB) in synaptosome-enriched fractions of rat brain was ascertained using a GLC technique. The stability of GHB in synaptosomes was evaluated by addition of various gamma-aminobutyric acid (GABA) transaminase (GABA-T) inhibitors, GHB, or ethosuximide to the homogenizing medium. Furthermore, changes in whole brain GHB levels were compared with those in the synaptosomal fraction in animals treated with GABA-T inhibitors, GABA, or ethosuximide. GHB was present in synaptosome-enriched fractions in concentrations ranging from 40 to 70 pmol/mg of protein. There was no evidence for redistribution, leakage, or metabolism of GHB during the preparation of synaptosomes. The elevations of whole brain GHB level associated with GABA-T or ethosuximide treatment were reflected by a parallel increase in synaptosomal GHB content. These data add to the growing evidence that GHB may have neurotransmitter or neuromodulator function. 相似文献