全文获取类型
收费全文 | 11715篇 |
免费 | 1296篇 |
国内免费 | 3篇 |
出版年
2023年 | 56篇 |
2022年 | 53篇 |
2021年 | 300篇 |
2020年 | 162篇 |
2019年 | 216篇 |
2018年 | 247篇 |
2017年 | 223篇 |
2016年 | 400篇 |
2015年 | 626篇 |
2014年 | 650篇 |
2013年 | 689篇 |
2012年 | 862篇 |
2011年 | 895篇 |
2010年 | 567篇 |
2009年 | 443篇 |
2008年 | 667篇 |
2007年 | 656篇 |
2006年 | 507篇 |
2005年 | 506篇 |
2004年 | 497篇 |
2003年 | 435篇 |
2002年 | 425篇 |
2001年 | 172篇 |
2000年 | 182篇 |
1999年 | 163篇 |
1998年 | 129篇 |
1997年 | 72篇 |
1996年 | 76篇 |
1995年 | 70篇 |
1994年 | 65篇 |
1993年 | 52篇 |
1992年 | 92篇 |
1991年 | 98篇 |
1990年 | 106篇 |
1989年 | 102篇 |
1988年 | 78篇 |
1987年 | 91篇 |
1986年 | 78篇 |
1985年 | 97篇 |
1984年 | 82篇 |
1983年 | 61篇 |
1982年 | 57篇 |
1981年 | 67篇 |
1979年 | 64篇 |
1978年 | 59篇 |
1977年 | 51篇 |
1975年 | 60篇 |
1973年 | 56篇 |
1972年 | 67篇 |
1970年 | 50篇 |
排序方式: 共有10000条查询结果,搜索用时 125 毫秒
991.
Kilduff LP Lewis S Kingsley MI Owen NJ Dietzig RE 《Journal of strength and conditioning research / National Strength & Conditioning Association》2007,21(2):378-384
The purpose of the present study was twofold: firstly, to assess the reliability of various body composition methods, and secondly, to determine the ability of the methods to estimate changes in fat-free mass (FFM) following creatine (Cr) supplementation. Fifty-five healthy male athletes (weight 78.3 +/- 10.3 kg, age 21 +/- 1 years) gave informed consent to participate in this study. Subjects' FFM was estimated by hydrostatic weighing (HW), air-displacement plethysmography (ADP), bioelectrical impedance analysis (BIA), near-infrared spectroscopy (NIR), and anthropometric measurements (ANTHRO). Measurements were taken on 2 occasions separated by 7 days to assess the reliability of the methods. Following this, 30 subjects returned to the laboratory for an additional test day following 7 days of Cr supplementation (20 g.d(-1) Cr + 140 g.d(-1) dextrose) to assess each method's ability to detect acute changes in FFM. In terms of reliability, we found excellent test-retest correlations for all 5 methods, ranging from 0.983 to 0.998 (p < 0.001). The mean biases for the 5 methods were close to 0 (range -0.1 to 0.3 kg) and their 95% limits of agreement (LOAs) were within acceptable limits (HW = -1.1 to 1.7 kg; ADP = -1.1 to 1.2 kg; BIA = -1.0 to 1.0 kg; NIR = -1.4 to 1.4 kg); however, the 95% LOAs were slightly wider for ANTHRO (-2.4 to 2.6 kg). Following Cr supplementation there was a significant increase in body mass (from 77.9 +/- 10.1 kg to 78.9 +/- 10.3 kg, p = 0.000). In addition, all 5 body composition techniques detected the change in FFM to a similar degree (mean change: HW = 0.9 +/- 0.6 kg; ADP = 0.9 +/- 0.6 kg; BIA = 0.9 +/- 0.6 kg; NIR = 0.8 +/- 0.5 kg; ANTHRO = 1.0 +/- 0.7 kg; intraclass correlation coefficient = 0.962). We conclude that between-day differences in FFM estimation were within acceptable limits, with the possible exception of ANTHRO. In addition, all 5 methods provided similar measures of FFM change during acute Cr supplementation. 相似文献
992.
The genome architecture of ciliates, including features such as nuclear dualism and large-scale genome rearrangements, impacts gene and genome evolution in these organisms. To better understand the structure of macronuclear chromosomes in ciliates with extensively processed chromosomes, a sample of complete macronuclear chromosomes was sequenced from three ciliate species: Metopus es (Class [Cl]: Armophorea), Nyctotherus ovalis (Cl: Armophorea), and Chilodonella uncinata (Cl: Phyllopharyngea). By cloning whole macronuclear chromosomes into a plasmid vector, we generated nine clones from each of M. es and C. uncinata, and 37 clones from N. ovalis. Analysis of these macronuclear chromosomes provides insight into the evolution of genome features such as chromosome content, gene structure, and genetic code. Phylogenetic patterns can be found in telomere structure and codon usage, which are both more similar in M. es and N. ovalis than C. uncinata. In addition, we provide evidence of lateral transfer of a bacterial endo-beta-mannanase gene onto a M. es chromosome and report the discovery of a 42-bp conserved sequence motif within N. ovalis untranslated regions. 相似文献
993.
Chilodonella uncinata, like all ciliates, contains two distinct nuclei in every cell: a germline micronucleus and a somatic macronucleus. During development of the macronucleus from a zygotic nucleus, the genome is processed in several ways, including elimination of internal sequences. In this study, we analyze micronuclear and macronuclear copies of beta-tubulin in C. uncinata and find at least four divergent paralogs of beta-tubulin in the macronucleus. We characterize the micronuclear version of one paralog and compare its internally eliminated sequences (IESs) with previously described IESs in this species. These comparisons reveal the presence of a conserved sequence motif within IESs. In addition, we compare the sequences of beta-tubulin from C. uncinata with other ciliates and to other alveolates in order to test the hypothesis that the mode of molecular evolution in ciliates obscures phylogenetic signal in protein-coding genes. We find that heterogeneous rates of substitution in beta-tubulin across ciliates result in unstable genealogies that are inconsistent with phylogenies based on small subunit rDNA genes and on ultrastructure. We discuss the implications of our findings for genome processing and protein evolution in ciliates. 相似文献
994.
995.
Fisher J Devraj K Ingram J Slagle-Webb B Madhankumar AB Liu X Klinger M Simpson IA Connor JR 《American journal of physiology. Cell physiology》2007,293(2):C641-C649
Traditionally, transferrin has been considered the primary mechanism for cellular iron delivery, despite suggestive evidence for additional iron delivery mechanisms. In this study we examined ferritin, considered an iron storage protein, as a possible delivery protein. Ferritin consists of H- and L-subunits, and we demonstrated iron uptake by ferritin into multiple organs and that the uptake of iron is greater when the iron is delivered via H-ferritin compared with L-ferritin. The delivery of iron via H-ferritin but not L-ferritin was significantly decreased in mice with compromised iron storage compared with control, indicating that a feedback mechanism exists for H-ferritin iron delivery. To further evaluate the mechanism of ferritin iron delivery into the brain, we used a cell culture model of the blood-brain barrier to demonstrate that ferritin is transported across endothelial cells. There are receptors that prefer H-ferritin on the endothelial cells in culture and on rat brain microvasculature. These studies identify H-ferritin as an iron transport protein and suggest the presence of an H-ferritin receptor for mediating iron delivery. The relative amount of iron that could be delivered via H-ferritin could make this protein a predominant player in cellular iron delivery. blood-brain barrier; iron transport; H-ferritin 相似文献
996.
Wu M Neilson A Swift AL Moran R Tamagnine J Parslow D Armistead S Lemire K Orrell J Teich J Chomicz S Ferrick DA 《American journal of physiology. Cell physiology》2007,292(1):C125-C136
Increased conversion of glucose to lactic acid associated with decreased mitochondrial respiration is a unique feature of tumors first described by Otto Warburg in the 1920s. Recent evidence suggests that the Warburg effect is caused by oncogenes and is an underlying mechanism of malignant transformation. Using a novel approach to measure cellular metabolic rates in vitro, the bioenergetic basis of this increased glycolysis and reduced mitochondrial respiration was investigated in two human cancer cell lines, H460 and A549. The bioenergetic phenotype was analyzed by measuring cellular respiration, glycolysis rate, and ATP turnover of the cells in response to various pharmacological modulators. H460 and A549 cells displayed a dependency on glycolysis and an ability to significantly upregulate this pathway when their respiration was inhibited. The converse, however, was not true. The cell lines were attenuated in oxidative phosphorylation (OXPHOS) capacity and were unable to sufficiently upregulate mitochondrial OXPHOS when glycolysis was disabled. This observed mitochondrial impairment was intimately linked to the increased dependency on glycolysis. Furthermore, it was demonstrated that H460 cells were more glycolytic, having a greater impairment of mitochondrial respiration, compared with A549 cells. Finally, the upregulation of glycolysis in response to mitochondrial ATP synthesis inhibition was dependent on AMP-activated protein kinase activity. In summary, our results demonstrate a bioenergetic phenotype of these two cancer cell lines characterized by increased rate of glycolysis and a linked attenuation in their OXPHOS capacity. These metabolic alterations provide a mechanistic explanation for the growth advantage and apoptotic resistance of tumor cells. oxygen consumption; oxidative phosphorylation; Warburg effect; real time 相似文献
997.
Fisher RS 《Neurochemical research》2007,32(2):177-186
Immunohistochemical methods were used to label singly and/or in combination glutamic acid decarboxylase (GAD, the sole synthesizing
enzyme for the inhibitory neurotransmitter γ-aminobutyric acid) and phosphate-activated glutaminase (GLN, a synthesizing enzyme
for glutamate) in neurons of lateral reticular nucleus (LRN) of thalamus of adult cats. (1) GAD- and GLN-immunoreactivity
(IR) exhibited matching regional patterns of organization within LRN. (2) GAD- and GLN-IR co-localized within most if not
all LRN neuronal cell bodies as shown by light microscopy. (3) GAD- and GLN-IR had distinct subcellular localizations in LRN
neurons as shown by correlative light/electron microscopy. LRN neurons are important conceptual models where strongly inhibitory
cells receive predominant excitatory glutamatergic afferents (from neocortex). Consistent with known actions of intermediary
astrocytes, LRN neurons demonstrate GLN enrichment synergistically coupled with glutamatergic innervation to supplement the
glutamate pool for GABA synthesis (via GAD) and for metabolic utilization (via the GABA shunt/tricarboxylic acid cycle) but
not, apparently, for excitatory neurotransmission.
Special issue dedicated to John P. Blass. 相似文献
998.
Banerjee R Sreetama S Saravanan KS Dey SN Mohanakumar KP 《Neurochemical research》2007,32(7):1238-1247
The potent parkinsonian neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is known to cause dopaminergic neurodegeneration
in nigrostriatal system. In the present study we investigated the nuclear morphology of cells in the substantia nigra pars
compacta (SNpc) region of rats following unilateral intranigral infusion of the active metabolite, 1-methyl-4-phenyl pyridinium
ion (MPP+), which resulted in a dose-dependent and prolonged dopamine depletion in the ipsilateral striatum. There appeared a substantial
loss of tyrosine hydroxylase immunoreactive neurons in the SNpc that received the neurotoxin. Specific nuclear staining with
Hoechst 33342 or acridine orange revealed bright pyknotic, shrunken, distorted nuclei and condensed chromatin with perinuclear
nucleolus respectively following visualization with the former and latter dyes in the ipsilateral SNpc, as compared to the
round, intact nuclei and centrally positioned nucleolus in the contralateral side. Ultrastructural details of the nucleus
under transmission electron microscope confirmed distorted nuclear organization with shrunken or condensed nuclei and disrupted
nuclear membrane. These features are typical of nucleus undergoing apoptosis, and suggest that MPP+ causes dopaminergic neuronal death through an apoptotic mode. Typical laddering pattern of genomic DNA isolated from the
ipsilateral SN in agarose gel electrophoresis conclusively established apoptosis following intranigral administration of MPP+ in rats.
Rebecca Banerjee and Sen Sreetama contributed equally to this paper. 相似文献
999.
Bleau AM Planque N Lazar N Zambelli D Ori A Quan T Fisher G Scotlandi K Perbal B 《Journal of cellular biochemistry》2007,101(6):1475-1491
Previous work had suggested that recombinant CCN3 was partially inhibiting cell proliferation. Here we show that native CCN3 protein secreted into the conditioned medium of glioma transfected cells indeed induces a reduction in cell proliferation. Large amounts of CCN3 are shown to accumulate both cytoplasmically and extracellularly as cells reach high density, therefore highlighting new aspects on how cell growth may be regulated by CCN proteins. Evidence is presented establishing that the amount of CCN3 secreted into cell culture medium is regulated by post-translational proteolysis. As a consequence, the production of CCN3 varies throughout the cell cycle and CCN3 accumulates at the G2/M transition of the cycle. We also show that CCN3-induced inhibition of cell growth can be partially reversed by specific antibodies raised against a C-terminal peptide of CCN3. The use of several clones expressing various portions of CCN3 established that the CT module of CCN3 is sufficient to induce cell growth inhibition. 相似文献
1000.
Hasnat A Bichenkova E Yu X Arnold JR Fisher J Fedorova O Andrews J 《Journal of biomolecular structure & dynamics》2007,25(3):253-270
In order to investigate the interaction between hTS protein and its cognate mRNA, a 29nt fragment of TS mRNA was synthesized. This region has been suggested as a putative stem-loop involved in translational autoregulation. The melting temperature of the 29ntRNA was 65 degrees C, suggesting that this region does indeed form a stem-loop. Fluorescence spectroscopy was used to monitor the RNA: hTS protein interaction [dissociation constant (K(d)) 3.9 +/- 0.8 nM; stoichiometry of binding 1dimeric hTS: 1RNA]. When hTS was titrated against FdUMP, this gave the expected stoichiometry of 1dimeric hTS: 1.7 FdUMP but in the presence of the 29ntRNA, the stoichiometry of binding changed to 1dimeric hTS: 1RNA: 1FdUMP. Experiments using methotrexate (MTX) gave a stoichiometry of 1dimeric hTS: 1MTX and in the presence of 29ntRNA, the stoichiometry was unchanged. (19)F-NMR spectra of human TS: FdUMP complexes were found to be strikingly similar to analogous NMR spectra of complexes formed by L.casei TS and mouse TS. In the presence of FdUMP, spectra exhibited two additional resonances (-1.50 ppm and -34.4 ppm). The resonance at -1.50 ppm represents non-covalently bound FdUMP, the peak at -34.4 ppm represents covalently bound FdUMP. The addition of methotrexate to the binary TS-FdUMP complex caused a displacement of the internal equilibrium, with only the covalently-bound form seen, and with a slightly disturbed (19)F chemical shift (-36.5 ppm). Similar results were found when MTX was replaced by folinic or folic acid. The addition of 29ntRNA caused no changes to the (19)F spectra of either the binary or ternary complexes. 相似文献