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951.
Conventional two‐dimensional (2D) monolayer cultures of HepaRG cells allow in vitro maintenance of many liver‐specific functions. However, cellular dedifferentiation and functional deterioration over an extended culture period in the conventional 2D HepaRG culture have hampered its applications in drug testing. To address this issue, we developed tethered spheroids of HepaRG cells on Arg–Gly–Asp (RGD) and galactose‐conjugated substratum with an optimized hybrid ratio as an in vitro three‐dimensional (3D) human hepatocyte model. The liver‐specific gene expression level and drug metabolizing enzyme activities in HepaRG‐tethered spheorids were markedly higher than those in 2D cultures throughout the culture period of 7 days. The inducibility of three major cytochrome P450 (CYP) enzymes, namely CYP1A2, CYP2B6 and CYP3A4, was improved in both mRNA and activity level in tethered spheroids. Drug‐induced cytotoxic responses to model hepatotoxins (acetaminophen, chlorpromazine and ketoconazole) in tethered spheroids were comparable to 2D cultures as well as other studies in the literature. Our results suggested that the HepaRG‐tethered spheroid would be an alternative in vitro model suitable for drug safety screening. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   
952.
Retinoid X receptor (RXR) antagonists, including some environmental endocrine disruptors, have a teratogenic effect on vertebrate embryos. To investigate the toxicological mechanism on the protein expression level, a quantitative proteomic study was conducted to analyze the proteome alterations of zebrafish (Danio rerio) embryos exposed to gradient concentrations of a representative RXR antagonist UVI3003. Using isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling coupled nano high‐performance liquid chromatography‐tandem mass spectrometry (nano HPLC‐MS/MS), in total 6592 proteins were identified, among which 195 proteins were found to be differentially expressed by more than a two‐fold change in exposed groups compared with the control. Gene ontology analysis showed that these differential proteins were mostly involved in anatomical structure development, biosynthetic process, ion binding and oxidoreductase activity. Moreover, the biological pathways of translation, lipoprotein metabolism, cell survival and gluconeogenesis were intensively inhibited after exposure. Some significantly downregulated proteins such as apolipoprotein A‐I and vitellogenin and upregulated proteins such as calcium activated nucleotidase 1b, glutathione S‐transferase and glucose 6‐dehydrogenases showed a strong dose‐dependent response. The results provided new insight into the molecular details of RXR antagonist‐induced teratogenicity and added novel information of pathways and potential biomarkers for evaluation of RXR interfering activity. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
953.
No reflow after reperfusion therapy for myocardial infarction is a strong predictor of clinical outcome. Increased levels of inflammatory factors, including C‐reactive protein (CRP), in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) may affect myocardial perfusion. However, why the no‐reflow phenomenon increases in inflammation stress after PCI is not clear. The aim of the present study was to determine the effects and molecular mechanisms underlying the effects of CRP on the expression of cyclo‐oxygenase (COX) on the development of the no‐reflow phenomenon. There was a significant increase in plasma levels of CRP and interleukin (IL)‐6 in no‐reflow patients, suggesting that inflammatory factors play an important role in the development of the no‐reflow phenomenon. The mechanisms involved were further evaluated after reperfusion in a rat model mimicking the no‐reflow phenomenon. Compared with normal reflow rats, there were significant increases in both COX‐1 and COX‐2 in cardiac tissue from no‐reflow rats. The COX inhibitor indomethacin (5 mg/kg, i.p.) significantly reduced the no‐reflow area. In another series of experiments, human coronary artery endothelial cells (HCAEC) were treated with CRP at clinically relevant concentrations (5–25 μg/mL). C‐Reactive protein significantly increased COX‐1 and COX‐2 levels in a time‐ and concentration‐dependent manner. In addition, extracellular signal‐regulated kinase (ERK) and Jun N‐terminal kinase (JNK) were activated in CRP (5, 10, 25 μg/mL)‐treated HCAEC cultures. Furthermore, the ERK inhibitor pd98059 (30 μmol/L) and the JNK inhibitor sp600125 (10 μmol/L) blocked CRP‐induced COX‐1 and COX‐2 expression for 12 h. Together, the findings of the present study suggest that CRP can promote the development of the no‐reflow phenomenon by increasing COX‐1 and COX‐2 expression, which is regulated, in part, via ERK and JNK activity.  相似文献   
954.
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956.

Purpose

The associations between specific carotenoid intake and colorectal cancer risk remain inconsistent. The aim of this study was to examine the association between specific dietary carotenoid intake with colorectal cancer risk in Chinese adults.

Method

From July 2010 to October 2013, 845 eligible colorectal cancer cases and 845 frequency-matched controls (age and sex) completed in-person interviews. A validated food frequency questionnaire was used to estimate dietary intake. Multivariate logistical regression models were used to calculate the odds ratio (OR) and 95 % confidence intervals (95 % CIs) of colorectal cancer risk after adjusting for various confounders.

Results

A strong inverse association was found between β-cryptoxanthin intake and colorectal cancer risk. Compared with the lowest quartile, the highest quartile intake showed a risk reduction of 77 % (OR 0.23, 95 % CI 0.17–0.33, P trend < 0.01) after adjustment for various confounding variables. The inverse associations were also observed for α-carotene (OR 0.50, 95 % CI 0.37–0.68, P trend < 0.01), β-carotene (OR 0.67, 95 % CI 0.49–0.91, P trend < 0.01), and lycopene (OR 0.51, 95 % CI 0.37–0.70, P trend < 0.01). There was no statistically significant association between lutein/zeaxanthin intake and colorectal cancer risk. These findings were consistent across cancer site, sources of controls, and smoking status. The inverse associations between dietary α-carotene, β-cryptoxanthin, and lycopene intake and colorectal cancer risk were found in both males and females, while inverse associations between β-carotene intake and colorectal cancer risk were only observed in males.

Conclusions

Consumption of α-carotene, β-carotene, β-cryptoxanthin, and lycopene was inversely associated with colorectal cancer risk. No significant association was found between lutein/zeaxanthin intake and colorectal cancer risk.
  相似文献   
957.
Heteroatom-doped carbon dots (CDs) with excellent optical characteristics and negligible toxicity have emerged in many applications including bioimaging, biosensing, photocatalysis, and photothermal therapy. The metal-doping of CDs using various heteroatoms results in an enhancement of the photophysics but also imparts them with multifunctionality. However, unlike nonmetal doping, typical metal doping results in low fluorescence quantum yields (QYs), and an unclear photoluminescence mechanism. In this contribution, we detail results concerning zinc doped CDs (Zn-CDs) with QYs of up to 35%. The zinc ion charges serve as a surface passivating agent and prevent the aggregation of graphene π–π stacking, leading to an increase in the QY of the Zn-CDs. Structural and chemical investigations using spectroscopic and first principle simulations further revealed the effects of zinc doping on the CDs. The robust Zn-CDs were used for the ultra-trace detection of Hg2+ with a detection limit of 0.1 μM, and a quench mechanism was proposed. The unique optical properties of the Zn-CDs have promise for use in applications such as in vivo sensing and future phototherapy applications.

Zinc ions, acting as a surface passivating agent, prevented the aggregation of graphene π–π stacking and increased the quantum yield of Zn-carbon dots.  相似文献   
958.
Previously we synthesized redox sensitive polyurethane micelles, core crosslinked by diisocyanates (PU-CCL). To improve the intracellular drug release and tumor cellular toxicity of anticancer drugs loaded into polyurethane micelles, we now describe redox sensitive polyurethane micelles with tunable surface charge switchabilities, crosslinked with pH cleavable Schiff bonds, as anticancer drug carriers. Different amounts of 1,6-diaminohexane were connected onto the pendant carboxyl groups of amphiphilic multi-blocked polyurethane (PU-SS-COOH), resulting in polyurethanes with various ratios of pendant carboxyl and amine groups (denoted as PU-SS-COOH-NH2-1, PU-SS-COOH-NH2-2 and PU-SS-COOH-NH2-3). The surface charge switched as the pH was increased for PU-SS-COOH-NH2-1, PU-SS-COOH-NH2-2 and PU-SS-COOH-NH2-3. Then the PU-SS-COOH-NH2-3 micelles, dissolved in water, were crosslinked by glutaraldehyde resulting in surface charge switchable and reduction responsive polyurethane micelles with acid cleavable crosslinks (PU-ACCL). The crosslinked polyurethane micelles (PU-ACCL) demonstrated superior particle stability in phosphate buffered saline (PBS, pH = 7.4) solution without reducing agents, whereas the drug release rate was markedly accelerated by the addition of glutathione (GSH). Notably, the drug release from PU-ACCL was further accelerated in acidic fluid as the result of acid induced cleavage of the crosslinks. In vitro cytotoxicity studies demonstrated that doxorubicin (DOX)-loaded PU-ACCL micelles displayed increased cytotoxicity against tumor cells which was comparable to that obtained for DOX loaded into uncrosslinked polyurethane micelles. The reduction responsive and surface charge switchable polyurethane micelles with acid cleavable crosslinks, which have superior extracellular stability and provide rapid intracellular drug release, may hold great potential as a bio-triggered drug delivery system for cancer therapy.

Previously we synthesized redox sensitive polyurethane micelles, core crosslinked by diisocyanates (PU-CCL).  相似文献   
959.
Mercury species have aroused wide concern in the past several decades due to their high toxicity. However, it is still difficult to detect ultra-trace mercury species due to their biochemical transformation in complex samples. To establish a simpler and more sensitive method for pre-concentration and determination of trace mercury species, molybdenum disulfide (MoS2) nanosheets with sulfur-rich characteristics and enlarged interlayer spacing were prepared by a hydrothermal method coupled with a sonication-assisted liquid exfoliation method and acted as solid-phase extraction adsorbent. The nano-MoS2 had high adsorption capacity, fast adsorption rate and excellent selectivity towards mercury ions (Hg2+), methyl mercury (MeHg+) and ethyl mercury (EtHg+) in a wide pH range and complex matrices. And it could be easily regenerated by 4 mol L−1 HCl and reused several times. After optimizing HPLC-UV-HG-AFS conditions, a great linearity (1.0–10.0 μg L−1, R2 = 0.999 for Hg2+, MeHg+ and EtHg+), lower detection limits (0.017, 0.037 and 0.021 ng mL−1 for Hg2+, MeHg+ and EtHg+, respectively), relative standard deviations (<5%) and addition recoveries of the samples within 82.75–113.38% were observed. In summary, trace inorganic and organic mercury species in environmental and biological samples could be selectively enriched by the prepared nano-MoS2 and efficiently seperated and detected by HPLC-UV-HG-AFS. The present study will help provide a better strategy for environmental monitoring and health assessment of mercury pollutants.

As-synthesized few-layered molybdenum disulfide nanosheets were used as solid-phase extraction absorbent for ultra-trace mercury speciation analysis by HPLC-UV-HG-AFS.  相似文献   
960.
SrTiO3/NaTaO3 (STO/NTO) heterojunction photocatalysts were successfully constructed by decorating NaTaO3 nanocubes with SrTiO3 nanoparticles via a hydrothermal method. The structure of the perovskites NaTaO3 and SrTiO3 bear some resemblance to each other, which increases the interface lattice match for promoting the migration of photogenerated carriers between the STO/NTO interfaces. In comparison to pristine NaTaO3 and SrTiO3 samples, the STO/NTO composites exhibited remarkably improved capacity for the degradation of rhodamine B (RhB) under ultraviolet (UV) light (λ < 400 nm) irradiation. Furthermore, the partial replacement of O2− by N3− in the TaO 6 octahedron narrowed the band gap of NaTaO3, which significantly enhanced the photocatalytic performance of the SrTiO3/NaTaO3:N (STO/NTON) heterojunction under visible light (λ > 400 nm). Finally, the possible band structures of the STO/NTO and STO/NTON photocatalysts were proposed, which indicated that an n–n type heterojunction was constructed with a staggered gap for fast separation of photogenerated electron–hole pairs.

Novel SrTiO3/NaTaO3 and visible-light-driven SrTiO3/NaTaO3:N nano-heterojunctions with high interface–lattice match were synthesized for efficient photocatalytic removal of organic dye.  相似文献   
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