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971.
Koji Matsuo Suguru Yamamoto Takuya Wakamatsu Yoshimitsu Takahashi Kazuko Kawamura Yoshikatsu Kaneko Shin Goto Junichiro J. Kazama Ichiei Narita 《Toxins》2015,7(8):3155-3166
One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1β, IS 1.0 mM: 101.8 ± 21.8 pg/mL vs. 0 mM: 7.0 ± 0.3 pg/mL, TNF-α, IS 1.0 mM: 96.6 ± 11.0 pg/mL vs. 0 mM: 15.1 ± 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% ± 7.3% vs. 0 mM: 43.5% ± 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD. 相似文献
972.
Jaesuk Yun Eunyong Chung Ki Hwan Choi Dae Hyun Cho Yun Jeong Song Kyoung Moon Han Hey Jin Cha Ji Soon Shin Won-Keun Seong Young-Hoon Kim Hyung Soo Kim 《Biomolecules & therapeutics.》2015,23(4):386-389
Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation. 相似文献
973.
The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits 下载免费PDF全文
Michelle Khai Khun Yap Nget Hong Tan Si Mui Sim Shin Yee Fung Choo Hock Tan 《Basic & clinical pharmacology & toxicology》2015,117(4):274-279
The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab′)2] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab′)2 and venom antigens, as the terminal half‐life and volume of distribution of the F(ab′)2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence. 相似文献
974.
Quantitative Relationships Between the Cytotoxicity of Flavonoids on the Human Breast Cancer Stem‐Like Cells MCF7‐SC and Their Structural Properties 下载免费PDF全文
Hyeryoung Jung Soon Young Shin Yearam Jung Thao Anh Tran Hye Ok Lee Kang‐Yeoun Jung Dongsoo Koh Somi Kim Cho Yoongho Lim 《Chemical biology & drug design》2015,86(4):496-508
As some breast cancer‐related deaths can be attributed to the metastasis of cancer stem cells, chemotherapeutic agents targeting breast cancer stem cells are of interest as a potential treatment. Flavonoids that exhibit cytotoxicity on breast cancer stem cells have rarely been observed. Thus, the objective of this study was to measure potential cytotoxic effects of 42 different flavonoids on the human breast cancer stem‐like cell line, MCF7‐SC. The relationship between flavonoid structural properties and cytotoxicity has not been reported previously; therefore, we determined quantitative structure–activity relationships using both comparative molecular field analysis and comparative molecular similarity analysis. Further biological experiments including Western blot analysis, flow cytometry, and immunofluorescence microscopy were also conducted on the most cytotoxic 8‐chloroflavanone. 相似文献
975.
Zhenxing Yu Junjie Wang Na Zhang Jungwoo Shin Qiye Zheng Subing Qu Xiaoqing He Angus Rockett Hong Yang Paul V. Braun 《RSC advances》2018,8(68):38745
Here we show that dendritic architectures are attractive as the basis of hierarchically structured battery electrodes. Dendritically structured FeS2, synthesized via simple thermal sulfidation of electrodeposited dendritic α-Fe, was formed into an electrode and cycled vs. lithium. The reversible capacities of the dendritic FeS2 cathode were 560 mA h g−1 at 0.5C and 533 mA h g−1 at 1.0C after 50 cycles over 0.7–3.0 V. Over 0.7–2.4 V, where the electrode is more stable, the reversible capacities are 348 mA h g−1 at 0.2C and 179 mA h g−1 at 1.0C after 150 cycles. The good cycling performance and high specific capacities of the dendritic FeS2 cathodes are attributed to the ability of a dendritic structure to provide good ion and electron conducting pathways, and a large surface area. Importantly, the dendritic structure appears capable of accommodating volume changes imposed by the lithiation and delithiation process. The presence of a Li2−xFeS2 phase is indicated for the first time by high-resolution transmission electron microscopy (HRTEM) and scanning transmission electron microscopy (STEM) electron energy loss spectroscopy (EELS). We suspect this phase is what enables electrochemical cycling to possess high reversibility over 0.7–2.4 V.High performance dendritically structured FeS2 cathodes are systemically studied. The dendritic structure is resistant to volume changes during cycling, increasing cyclability. The presence of Li2–xFeS2, which also enhances cyclability, is confirmed. 相似文献
976.
Kazuo Tarao Akito Nozaki Makoto Chuma Masataka Taguri Shin Maeda 《World journal of hepatology》2021,13(1):144-150
BACKGROUND The oral nucleos(t)ide analogue,entecavir(ETV) was demonstrated to reduce the rate of hepatocellular carcinoma(HCC) in patients with hepatitis B virus(HBV)-associated liver cirrhosis.However,the reduction of HCC differs in various regions of the world.AIM To investigate the reduction of HCC development due to ETV therapy by metaanalysis.METHODS We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed(2004-2019).RESULTS The regions with the most marked reduction in HCC development due to ETV therapy were Spain(1.0 %/year) and Canada(Southern part,1.3 %/year),and the most ineffective areas were South Korea(3.6 %-3.8 %/year),China(3.3 %/year),Taiwan(2.4 %-3.1 %/year),and Hong Kong(2.8 %/year).Following ETV administration,the incidence of HCC in genotype D regions(1.89 %±0.28 %/year,mean ± SE) was significantly lower than that in genotype C regions(2.91%±0.24%/year,P 0.01).With regard to the initial HBV-DNA level,in genotype C patients(average:5.61 Log_(10)IU/mL) this was almost the same as that in genotype D patients(average:5.46 Log_(10)IU/mL).Moreover,there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment.CONCLUSION The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent. 相似文献
977.
Marked mitochondrial DNA sequence heterogeneity in single CD34+ cell clones from normal adult bone marrow 下载免费PDF全文
Somatic mitochondrial DNA (mtDNA) mutations accumulate with age in postmitotic tissues but have been postulated to be diluted and lost in continually proliferating tissues such as bone marrow (BM). Having observed marked sequence variation among healthy adult individuals' total BM cell mtDNA, we undertook analysis of the mtDNA control region in a total of 611 individual CD34+ clones from 6 adult BM donors and comparison of these results with the sequences from 580 CD34+ clones from 5 umbilical cord blood (CB) samples. On average, 25% (range, 11% to 50%) of individual CD34+ clones from adult BM showed mtDNA heterogeneity, or sequence differences from the aggregate mtDNA sequence of total BM cells of the same individual. In contrast, only 1.6% of single CD34+ clones from CB showed mtDNA sequence variation from the aggregate pattern. Thus, age-dependent accumulation of mtDNA mutations appears relatively common in a mitotically active human tissue and may provide a method to approximate the mutation rate in mammalian cells, to assess the contribution of reactive oxygen species to genomic instability, and for natural "marking" of hematopoietic stem cells; our data also have important implications for the aging process, forensic identifications, and anthropologic conclusions dependent on the mtDNA sequence. 相似文献
978.
E. Shiba Seung Jin Kim Tetsuya Taguchi Masaaki Izukura Tetsuro Kobayashi Junkoh Furukawa Eiji Yayoi Eisei Shin Yuichi Takatsuka Hiroki Koyama Shin-ichiro Takai 《Journal of cancer research and clinical oncology》1997,123(10):555-559
Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis
and is presumed to play a key role in extracellular proteolysis and facilitate the migration of cancer cells. This study was
conducted prospectively to evaluate the prognostic significance of u-PA antigen level in breast cancer tissues. u-PA concentrations
in the cytosol of 226 breast cancer tissues were determined prospectively by enzyme-linked immunosorbent assay using cytosol
fractions prepared for steroid hormone assay. The median follow-up period of the patients was 60 months. Various prognostic
factors were evaluated by univariate analysis or multivariate analysis using the Cox proportional-hazards method. Patients
with primary breast cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients
with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent risk factor for disease-free
survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors,
a high u-PA antigen level, lymph node involvement, and a positive estrogen receptor status were the most important for predicting
relapse-free survival (P=0.044, P<0.0001, P=0.0039). This first prospective study confirmed the prognostic significance of the u-PA antigen level in association with
other major prognostic factors. The results of our present study suggest that u-PA in breast cancer tissue might be involved
in breast cancer invasion and metastasis.
Received: 20 November 1996 / Accepted: 9 June 1997 相似文献
979.
Jaffar M. Khan BM BCh Robert J. Lederman MD 《Catheterization and cardiovascular interventions》2018,91(6):1052-1053
- Transcatheter electrosurgery has emerging value in a range of other new procedures that require traversing tissue (transcaval access, transcatheter Glenn Shunt) or slicing tissue (LAMPOON slicing of the mitral valve and BASILICA slicing of the aortic valve).
- This is the first report of bipolar radiofrequency wires used to cross lesions in humans, reported here in seven re‐entry CTO cases.
- The bipolar configuration may provide directionality to charge without need for wire alignment and advancement, but is theoretically disadvantageous for tissue “cutting” because of problems with charge concentration.
980.
Yong Chan Shin Jin-Young Jang Ye Rim Chang Woohyun Jung Wooil Kwon Hongbeom Kim Eunjung Kim Sun-Whe Kim 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2019,21(1):51-59