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971.
Adaikkappan Periyakaruppan Shubhashish Sarkar Prabakaran Ravichandran Bindu Sadanandan Chidananda S. Sharma Vani Ramesh Joseph C. Hall Renard Thomas Bobby L. Wilson Govindarajan T. Ramesh 《Archives of toxicology》2009,83(6):595-600
Uranium is a naturally occurring radioactive material present everywhere in the environment. It is toxic because of its chemical
or radioactive properties. Uranium enters environment mainly from mines and industry and cause threat to human health by accumulating
in lungs as a result of inhalation. In our previous study, we have shown the effectiveness of antioxidant system response
to the oxidative stress induced by uranyl acetate (UA) in rat lung epithelial (LE) cells. As part of our continuing studies;
here, we investigated the mechanism underlying when LE cells are exposed to different concentration of UA. Oxidative stress
may lead to apoptotic signaling pathways. LE cells treated with 0.25, 0.5 and 1 mM of UA results in dose and time-dependent
increase in activity of both caspases-3 and -8. Increase in the concentration of cytochrome-c oxidase in cytosol was seen
in LE cells treated with 1 mM UA as a result of mitochondria membrane permeability. The cytochrome-c leakage may trigger the
apoptotic pathway. TUNEL assay performed in LE cells treated with 1 mM of UA showed significant incorporation of dNTPs in
the nucleus after 24 h. In the presence of the caspase inhibitors, we observed the significant decrease in the activity of
caspases-8 and -3 in 0.5 and 1 mM UA-treated LE cells. 相似文献
972.
973.
Kadambari Ramani Subashini Kaliaperumal Sandip Sarkar Sujatha Sistla 《Korean journal of ophthalmology : KJO》2021,35(4):318
PurposeThe objective of the study was to evaluate the type of conjunctival microbial flora in intensive care unit patients and their antimicrobial sensitivity pattern.MethodsA total of 272 samples (conjunctival swabs) were taken from patients in various intensive care units and sent for culture and sensitivity. An ocular examination was done to look for lagophthalmos, conjunctival discharge, exposure keratitis, and corneal perforation.ResultsMajority (82.1%) of the samples showed at least one microbial isolate while 29 (10.7%) samples showed multiple microbial growth. The most common microbes were coagulase negative Staphylococcus spp. (41.5% of isolates), diphtheroids (11.0% of isolates), and Staphylococcus aureus (9.6% of isolates) which are the usual commensals of the ocular surface. Of the other microbes isolated, Pseudomonas aeruginosa (4.0%) was the most common. Eighty-four percent isolates of coagulase negative Staphylococcus sp., 81.8% isolates of diphtheroids and 100% isolates of Staphylococcus aureus were penicillin resistant. All isolates of Enterococcus fecalis were sensitive only to vancomycin. Two hundred and twenty eyes (80.9%) had varying degrees of lagophthalmos. Nineteen (7.0%) had severe corneal exposure changes leading to infectious corneal ulcer and perforation in all of them.ConclusionsThe isolates in patients of intensive care units were no different from the normal conjunctival flora though few pathogenic organisms such as Pseudomonas aeruginosa and Acinetobacter sp. were also isolated. Most of the isolates were penicillin resistant. This knowledge will help take appropriate prophylactic measures to contain ocular infections in the intensive care units. 相似文献
974.
975.
In the past few years progress has been made in understanding the molecular mechanisms that underlie the initial generation, and the ensuing differentiation and maintenance, of humoral and cellular immunity. Although B and T cell immunological memory contribute to protective immunity through fundamentally distinct effector functions, interesting analogies are becoming apparent between the two memory compartments. These include heterogeneity in function, anatomical location and phenotype, which probably relate to differential environmental cues during the early priming events as well as the later differentiation phases. Detailed definition of the molecular and cellular signals involved in the development of immunological memory, and the relative contributions of different memory subsets to protective immunity, remains an important goal. 相似文献
976.
Amar K. Chandra Aparajita Chatterjee Rituparna Ghosh Mahitosh Sarkar 《Food and chemical toxicology》2010
Excess chromium (Cr) exposure is associated with various pathological conditions including reproductive dysfunction. Generation of oxidative stress is one of the plausible mechanisms behind Cr induced cellular deteriorations. The efficacy of vitamin E to combat Cr induced oxidative damage in adult rat testis has investigated in the current study. Adult male rats exposed to hexavalent Cr (intraperitoneal injection with 0.4 mg K2Cr2O7/kg bw/day) for 26 days resulted in decreased accessory sex organs weight compared to controls. Development of oxidative stress in testis was evidenced by increased lipid peroxidation along with decreased superoxide dismutase (SOD) and catalase activities than control animals. Marked reduction in the activities of testicular steroidogenic enzymes; Δ53β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, serum testosterone and Leutinizing Hormone (LH) levels were observed. However significant increase in serum Follicle Stimulating Hormone (FSH) level was observed with Cr treated group. Histological evaluation of testis revealed degeneration of stage VII spermatogenic cycle along with decrease in epithelial cell height in epididymis and seminiferous tubules; number of different germ cells per seminiferous tubule and seminiferous tubular diameter reduced after Cr exposure. Simultaneous oral supplementation of vitamin E (50 mg/kg bw/day) in Cr exposed rats showed less oxidative damage and restored the otherwise altered testicular activities. Epididymal sperm number was also restored in vitamin E-supplemented group than Cr induced rats. This study implicates vitamin E as a possible protective agent against Cr induced spermatogenic and steroidogenic alteration. 相似文献
977.
Muniasamy Neerathilingam David E. Volk Swapna Sarkar Todd M. Alam M. Kathleen Alam G.A. Shakeel Ansari Bruce A. Luxon 《Toxicology letters》2010
Tributyl phosphate (TBP) is a toxic organophosphorous compound widely used in many industrial applications, including significant usage in nuclear processing. The industrial application of this chemical is responsible for occupational exposure and environmental pollution. In this study, 1H NMR-based metabonomics has been applied to investigate the metabolic response to TBP exposure. Male Sprague-Dawley rats were given a TBP-dose of 15 mg/kg body weight, followed by 24 h urine collection, as was previously demonstrated for finding most of the intermediates of TBP. High-resolution 1H NMR spectroscopy of urine samples in conjunction with statistical pattern recognition and compound identification allowed for the metabolic changes associated with TBP treatment to be identified. Discerning NMR spectral regions corresponding to three TBP metabolites, dibutyl phosphate (DBP), N-acetyl-(S-3-hydroxybutyl)-l-cysteine and N-acetyl-(S-3-oxobutyl)-l-cysteine, were identified in TBP-treated rats. In addition, the 1H NMR spectra revealed TBP-induced variations of endogenous urinary metabolites including benzoate, urea, and trigonelline along with metabolites involved in the Krebs cycle including citrate, cis-aconitate, trans-aconitate, 2-oxoglutarate, succinate, and fumarate. These findings indicate that TBP induces a disturbance to the Krebs cycle energy metabolism and provides a biomarker signature of TBP exposure. We show that three metabolites of TBP, dibutylphosphate, N-acetyl-(S-3-hydroxybutyl)-l-cysteine and N-acetyl-(S-3-oxobutyl)-l-cysteine, which are not present in the control groups, are the most important factors in separating the TBP and control groups (p < 0.0023), while the endogenous compounds 2-oxoglutarate, benzoate, fumarate, trigonelline, and cis-aconetate were also important (p < 0.01). 相似文献
978.
Zhiwei Wang Yiwei Li Aamir Ahmad Asfar S. Azmi Dejuan Kong Sanjeev Banerjee Fazlul H. Sarkar 《Drug Resistance Updates》2010,13(4-5):109-118
Although chemotherapy is an important therapeutic strategy for cancer treatment, it fails to eliminate all tumor cells due to intrinsic or acquired drug resistance, which is the most common cause of tumor recurrence. Emerging evidence suggests an intricate role of cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT)-type cells in anticancer drug resistance. Recent studies also demonstrated that microRNAs (miRNAs) play critical roles in the regulation of drug resistance. Here we will discuss current knowledge regarding CSCs, EMT and the role of regulation by miRNAs in the context of drug resistance, tumor recurrence and metastasis. A better understanding of the molecular intricacies of drug-resistant cells will help to design novel therapeutic strategies by selective targeting of CSCs and EMT-phenotypic cells through alterations in the expression of specific miRNAs towards eradicating tumor recurrence and metastasis. A particular promising lead is the potential synergistic combination of natural compounds that affect critical miRNAs, such as curcumin or epigallocatechin-3-gallate (EGCG) with chemotherapeutic agents. 相似文献
979.
Glioma cells in situ are surrounded by microglia, suggesting the potential of glioma-microglia interactions to produce various outcomes. As chemokines are important mediators of cell-cell communication, we sought first to identify commonly expressed chemokines in 16 human glioma lines. We found CCL2 (macrophage chemoattractant protein-1) messenger RNA to be expressed by the majority of glioma lines. However, these lines did not express the CCL2 receptor, CCR2, which was found on microglia. Next, we overexpressed CCL2 in the U87 glioma line, which has low basal level of CCL2, to investigate the hypothesis that glioma-secreted CCL2 interacts with microglia to affect glioma growth. Stable clones with 10- to 12-fold elevation of CCL2 have similar growth rate and invasive capacity as vector controls when cultured in isolation. However, in coculture with microglia in a three-dimensional collagen gel matrix, the invasiveness of CCL2-overexpressing clones was increased. Gene array analyses were then undertaken and they revealed that interleukin (IL)-6 was consistently increased in the coculture. Recombinant IL-6 enhanced the invasiveness of glioma cells when these were cultured alone, whereas a neutralizing antibody to IL-6 attenuated the microglia-stimulated glioma invasiveness. Finally, we found that human glioma specimens in situ contained IL-6 immunoreactivity that was expressed on CD68+ cells. This study has uncovered a mechanism by which glioma cells exploit microglia for increased invasiveness. Specifically, glioma-derived CCL2 acts upon CCR2-bearing microglia, which then produces IL-6 to stimulate gliomas. The CCL2/CCR2/IL-6 loop is a potential therapeutic target for the currently incurable malignant gliomas. 相似文献
980.
Zhiwei Wang Hiroyuki Inuzuka Jiateng Zhong Pengda Liu Fazlul H. Sarkar Yi Sun Wenyi Wei 《Oncotarget》2012,3(11):1294-1300
The Skp2 (S-phase kinase associated protein 2) oncoprotein is often highly expressed in various types of human cancers. However, the mechanistic basis of its oncogenic function, as well as the upstream regulatory pathway(s) that control Skp2 activities remains not fully understood. Recently, we reported that p300 acetylates Skp2 at two conserved lysine residues K68 and K71 within its NLS (Nuclear localization signal). This modification leads to increased Skp2 stability and cytoplasmic translocation, thus contributing to elevated Skp2 oncogenic potential. Moreover, we found that the SIRT3 tumor suppressor serves as the physiological deacetylase that antagonizes p300-mediated Skp2 acetylation. Furthermore, we showed that Skp2 governs E-cadherin ubiquitination and degradation in the cytosol. Consistent with this, we observed an inverse correlation between Skp2 and E-cadherin expression in clinical breast tumor samples. Therefore, our work elucidates a novel acetylation-dependent regulatory mechanism for Skp2 oncogenic functions. 相似文献