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941.
We have designed an immobilization bed that accommodates mice of all ages and sizes, to improve image registration for multimodal scans and for longitudinal preclinical imaging studies. Stationary pegs were placed such that they effectively immobilized mice and reduced set-up time. (22)Na fiducial markers were placed into the pegs at unique depths to provide 3D references to facilitate image registration. Multiple users registered positron emission tomographic (PET) and CT data obtained with and without the bed to examine the effect of the bed on registration accuracy and interuser variability. The image registrations performed by different users were evaluated for their similarity by using the Entropy Correlation Coefficient as a metric. The immobilization bed significantly reduced variations in body movement and interuser variability. Average differences in quantification of tumor PET signal among users when registering images without versus with the fiduciary-marker bed fell from 9.1% to 0.8% for maximal percentage injected dose per gram (%ID/g), from 15.6% to 2.3% for mean %ID/g, and from 9.4% to 0.7% for the 90th percentile of the maximum %ID/g. The bed improves animal immobilization, greatly reduces interuser variability, and supports registration of image data acquired from different imaging sessions. 相似文献
942.
Enhancing and sustaining AMG 009 dissolution from a matrix tablet via microenvironmental pH modulation and supersaturation,
where poorly soluble acidic AMG 009 molecule was intimately mixed and compressed together with a basic pH modifier (e.g., sodium carbonate) and nucleation inhibitor hydroxypropyl methylcellulose K100 LV (HPMC K100 LV), was demonstrated previously. However, not all acidic or basic drugs are compatible with basic or acidic pH
modifiers either chemically or physically. The objective of this study is to investigate whether similar dissolution enhancement
of AMG 009 can be achieved from a bilayer dosage form, where AMG 009 and sodium carbonate are placed in a separate layer with
or without the addition of HPMC K100 LV in each layer. Study results indicate that HPMC K100 LV-containing bilayer dosage
forms gained similar dissolution enhancement as matrix dosage forms did. Bilayer dosage forms without HPMC K100 LV benefitted
the least from dissolution enhancement. 相似文献
943.
Ali Reza Jafarnejadi Mehdi Homaee Gholamabbas Sayyad Mohammad Bybordi 《Soil & Sediment Contamination》2011,20(1):98-113
Cadmium (Cd) accumulation in edible crops is undesirable due to its hazardous influences on human health. The objectives of this study were: i) to evaluate the spatial variability of grain Cd and its relationships with soil properties in 4000 km2 wheat farms; ii) to evaluate the effect of wheat cultivar on the soil properties vs. grain Cd relationships. A number of 255 soil (0–20 cm) and grain samples were taken and Cd concentrations in grain samples and some soil properties were measured. Grain Cd concentrations in 95 percent of the samples exceeded the threshold of 0.2 mg kg?1. Durum wheat had more potential to accumulate Cd in grain (0.76 mg kg?1) than bread (0.69 mg kg?1). There was significant (p < 0.01) correlation between grain Cd and organic carbon (r = 0.66), CEC (r = 0.77) and DTPA-extractable Cd (p < 0.05) (r = 0.57) of the soils. Greater Pearson coefficient values for durum wheat showed that, in the studied calcareous soils, organic carbon, CEC, Cd-DTPA had more effects on durum wheat than bread wheat cultivar. The obtained Kriging map of grain Cd identified three hotspots at the east (durum wheat cultivation), the west (intensive irrigated wheat farms), and south (wheat farms around petrochemical industries) of the region. Agricultural mismanagement due to overusing P-fertilizers increased Cd concentration in the topsoils and grains of wheat farms in the study area. 相似文献
944.
Anwar J Shafique U Waheed-uz-Zaman un Nisa Z Munawar MA Jamil N Salman M Dar A Rehman R Saif J Gul H Iqbal T 《International journal of phytoremediation》2011,13(5):410-420
Adsorption is an environmental friendly process for removal and/or recovery of heavy metals from wastewater. In recent years, it has been substantiated as a popular technique to treat industrial waste effluents, with significant advantages. In this work, batchwise removal of chromium (III) ions from water by Polyalthia longifolia leaves was studied as a function of adsorbent dose, pH, contact time, and agitation speed. Surface characteristics of the leaves were evaluated by recording IR spectra. The Langmuir, Freundlich, and Temkin adsorption isotherms were employed to explain the sorption process. It was found that one gram of leaves can remove 1.87 mg of trivalent chromium when working at pH 3.0. It has been concluded that Polyalthia longifolia leaves can be used as cost-effective and benign adsorbents for removal of Cr(III) ions from wastewater. 相似文献
945.
Hamza TH Chen H Hill-Burns EM Rhodes SL Montimurro J Kay DM Tenesa A Kusel VI Sheehan P Eaaswarkhanth M Yearout D Samii A Roberts JW Agarwal P Bordelon Y Park Y Wang L Gao J Vance JM Kendler KS Bacanu SA Scott WK Ritz B Nutt J Factor SA Zabetian CP Payami H 《PLoS genetics》2011,7(8):e1002237
Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson''s disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP''s main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P2df = 10−6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10−7) but not in light coffee-drinkers. The a priori Replication hypothesis that “Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers” was confirmed: ORReplication = 0.59, PReplication = 10−3; ORPooled = 0.51, PPooled = 7×10−8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10−3), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10−13). Imputation revealed a block of SNPs that achieved P2df<5×10−8 in GWAIS, and OR = 0.41, P = 3×10−8 in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients. 相似文献
946.
Arezou Ghahghaei S. Zahra Bathaie Ali Shahraki Farzad Rahmany Asgarabad 《International journal of peptide research and therapeutics》2011,17(2):101-111
β-Casein is one of the major components of the milk micelles of most mammals and has been shown to exhibit in vitro chaperone-like
activity. Glycerol is a chemical chaperone belonging to the polyol family, which increases protein stability and inhibits
protein aggregation. These prompted us to compare the chaperone-like activity of β-casein and glycerol. In this study, the
effect of β-casein and glycerol on folding of the target proteins (ovotransferrin, insulin and α-lactalbumin) in the presence
of dextran, as a macromolecular crowding agent, is examined using visible absorption spectroscopy, intrinsic fluorescence
spectroscopy, 1-anilino-8-naphthalene sulfonic acid fluorescence binding and near CD spectroscopy. In the presence of dextran,
the rate and extent of aggregation of target proteins was enhanced and β-casein was less effective in preventing the aggregation
and precipitation of target proteins. These data support the hypothesis that β-casein interacts more effectively with slowly
aggregating rather than rapidly aggregating target proteins. It is proposed that dextran-induced changes to protein conformation
and the rate of intermolecular association are in a kinetic competition with the chaperoning action of β-casein; however our
results demonstrated the higher activity of glycerol, as a chemical chaperone, than β-casein on the folding of target proteins,
especially in the presence of dextran. This is likely due to the stabilizing effect of glycerol on protein structure and environment.
The implications for the in vivo functions of β-casein and glycerol, based on their exhibiting such in vitro chaperone-like
activities, are discussed. 相似文献
947.
Homocysteine thiolactone (HCTL) is a cyclic thioester of homocysteine, showing high reactivity toward lysine residues of proteins.
In the present study the structural properties and aggregation propensity of bovine pancreatic insulin were studied in the
presences of increasing concentration of HCTL (0–500 μM), using different spectroscopic techniques. As shown in this study,
HCTL induces gross structural alterations and subsequently aggregation of insulin in a dose dependent manner. Also induction
of insulin aggregation by HCTL occurs in a sequential process, where native protein with alpha-helical abundant structure
gradually transforms into partially folded conformations with the significant amount of beta-sheet. Since C-terminal B-chain
of insulin plays a critical role in stability of this protein, the structural alteration/aggregation induced by HCTL can be
consequence of homocysteinylation of the only Lysine residue (Lys29) on its B-chain. This study may have important implications
regarding the effect of HCTL on structure of insulin particularly in the pathological states linked to hyperhomocysteinemia. 相似文献
948.
The mitogen-activated protein kinase (MAPK) pathway is stimulated in differentiated chondrocytes and is an important signaling cascade for chondrocyte differentiation and survival. Pro-inflammatory cytokines such as interleukin 1β (IL-1β) play important roles in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In this study, we investigated whether curcumin and resveratrol can synergistically inhibit the catabolic effects of IL-1β, specifically the inhibition of the MAPK and subsequent apoptosis in human articular chondrocytes. Chondrocytes were either left untreated or treated with 10 ng/ml IL-1β or 1 μM U0126, a specific inhibitor of MAPK pathway alone for the indicated time periods or pre-treated with 10 μM curcumin, 10 μM resveratrol or 10 μM resveratrol and 10 μM curcumin for 4 h followed by co-treatment with 10 ng/ml IL-1β or 1 μM U0126 and 10 μM resveratrol, 10 μM curcumin or 10 μM resveratrol and 10 μM curcumin for the indicated time periods. Cultures were evaluated by immunoblotting and transmission electron microscopy. Incubation of chondrocytes with IL-1β resulted in induction of apoptosis, downregulation of β1-integrins and the extracellular signal-regulated kinase 1/2 (Erk1/2). Interestingly, U0126 induced apoptosis and blocked the above-mentioned proteins in a similar way to IL-1β. Furthermore, curcumin and resveratrol inhibited IL-1β- or U0126-induced apoptosis and downregulation of β1-integrins and Erk1/2 in human articular chondrocytes. These results suggest that combining these two natural compounds activates MEK/Erk signaling, a pathway that is involved in the maintenance of chondrocyte differentiation and survival. 相似文献
949.
Ali S Champagne DL Spaink HP Richardson MK 《Birth defects research. Part C, Embryo today : reviews》2011,93(2):115-133
Technological innovation has helped the zebrafish embryo gain ground as a disease model and an assay system for drug screening. Here, we review the use of zebrafish embryos and early larvae in applied biomedical research, using selected cases. We look at the use of zebrafish embryos as disease models, taking fetal alcohol syndrome and tuberculosis as examples. We discuss advances in imaging, in culture techniques (including microfluidics), and in drug delivery (including new techniques for the robotic injection of compounds into the egg). The use of zebrafish embryos in early stages of drug safety-screening is discussed. So too are the new behavioral assays that are being adapted from rodent research for use in zebrafish embryos, and which may become relevant in validating the effects of neuroactive compounds such as anxiolytics and antidepressants. Readouts, such as morphological screening and cardiac function, are examined. There are several drawbacks in the zebrafish model. One is its very rapid development, which means that screening with zebrafish is analogous to "screening on a run-away train." Therefore, we argue that zebrafish embryos need to be precisely staged when used in acute assays, so as to ensure a consistent window of developmental exposure. We believe that zebrafish embryo screens can be used in the pre-regulatory phases of drug development, although more validation studies are needed to overcome industry scepticism. Finally, the zebrafish poses no challenge to the position of rodent models: it is complementary to them, especially in early stages of drug research. 相似文献
950.
Jager M Chiori R Alié A Dayraud C Quéinnec E Manuel M 《Journal of experimental zoology. Part B. Molecular and developmental evolution》2011,(3):171-187
Ctenophores are non-bilaterian animals sharing with cnidarians and bilaterians the presence of sensory receptors, nerve cells, and synapses, absent in placozoans and sponges. Although recent immunofluorescence studies have renewed our knowledge of cnidarian neuro-anatomy, ctenophores have been much less investigated despite their importance to understanding the origin and early evolution of the nervous system. In this study, the neuro-anatomy of the ctenophore Pleurobrachia pileus (Müller, 1776) was explored by whole-mount fluorescent antibody staining using antibodies against tyrosylated -tubulin, FMRFamide, and vasopressin. We describe the morphology of nerve nets and their local specializations, and the organization of the aboral neuro-sensory complex comprising the apical organ and polar fields. Two distinct nerve nets are distinguished: a mesogleal nerve net, loosely organized throughout body mesoglea, and a much more compact “nerve net” with polygonal meshes in the ectodermal epithelium. The latter is organized as a plexus of short nerve cords. This epithelial nervous system contains distinct sub-populations of dispersed FMRFamide and vasopressin immunoreactive nerve cells. In the aboral neuro-sensory complex, our most significant observations include specialized nerve nets underlying the apical organ and polar fields, a tangential bundle of actin-rich fibers (interpreted as a muscle) within the polar fields, and distinct groups of neurons labeled by anti-FMRFamide and anti-vasopressin antibodies, within the apical organ floor. These results are discussed in a comparative perspective. 相似文献