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71.
Deepak K. Sharma Anil K. Tripathi Rashmi Sharma Reena Chib Reyaz ur Rasool Altaf Hussain Baldev Singh Anindya Goswami Inshad A. Khan Debaraj Mukherjee 《Medicinal chemistry research》2014,23(4):1643-1653
A series of bisindolylmethanes (BIMs) (1a–7j) including hybrid BIMs 6a–6c were prepared for bioevaluation. The results of initial antimicrobial screening of compounds 1a–6c showed compounds 2b, 2m, 4a and 5b to be the most potent inhibitors, exhibiting MIC as well as MBC values equal to or less than that of ciprofloxacin (0.5–2 μg/mL) against Staphylococcus aureus, MRSA and VRE. Compound 2m was selected further to study the effect of N,N′ disubstitution towards antibacterial and antitumor activity. It was observed that substitution at N,N′ position (7a–7j) of 2m diminishes its antibacterial activity though in vitro antitumour activity against a panel of prostate, cervical and lung cancer cell lines remains more or less intact. 相似文献
72.
73.
V. Kumar Uma Bhandari C. D. Tripathi Geetika Khanna 《Indian journal of pharmaceutical sciences》2014,76(4):315-322
Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na+/K+ ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na+/K+ ATPase activity and DNA laddering, visceral fat pad and organ''s weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus. 相似文献
74.
Clint D Kilts Ashley Kennedy Amanda L Elton Shanti Prakash Tripathi Jonathan Young Josh M Cisler G Andrew James 《Neuropsychopharmacology》2014,39(5):1135-1147
Cocaine and other drug dependencies are associated with significant attentional bias for drug use stimuli that represents a candidate cognitive marker of drug dependence and treatment outcomes. We explored, using fMRI, the role of discrete neural processing networks in the representation of individual differences in the drug attentional bias effect associated with cocaine dependence (AB-coc) using a word counting Stroop task with personalized cocaine use stimuli (cocStroop). The cocStroop behavioral and neural responses were further compared with those associated with a negative emotional word Stroop task (eStroop) and a neutral word counting Stroop task (cStroop). Brain–behavior correlations were explored using both network-level correlation analysis following independent component analysis (ICA) and voxel-level, brain-wide univariate correlation analysis. Variation in the attentional bias effect for cocaine use stimuli among cocaine-dependent men and women was related to the recruitment of two separate neural processing networks related to stimulus attention and salience attribution (inferior frontal–parietal–ventral insula), and the processing of the negative affective properties of cocaine stimuli (frontal–temporal–cingulate). Recruitment of a sensory–motor–dorsal insula network was negatively correlated with AB-coc and suggested a regulatory role related to the sensorimotor processing of cocaine stimuli. The attentional bias effect for cocaine stimuli and for negative affective word stimuli were significantly correlated across individuals, and both were correlated with the activity of the frontal–temporal–cingulate network. Functional connectivity for a single prefrontal–striatal–occipital network correlated with variation in general cognitive control (cStroop) that was unrelated to behavioral or neural network correlates of cocStroop- or eStroop-related attentional bias. A brain-wide mass univariate analysis demonstrated the significant correlation of individual attentional bias effect for cocaine stimuli with distributed activations in the frontal, occipitotemporal, parietal, cingulate, and premotor cortex. These findings support the involvement of multiple processes and brain networks in mediating individual differences in risk for relapse associated with drug dependence. 相似文献
75.
Monika Tripathi Vianney Regnier Zakaria Ziani Marc Devillard Christian Philouze David Martin 《RSC advances》2018,8(67):38346
Oxidation of vinamidinium salts with meta-chloroperbenzoic acid is the key synthetic step towards new persistent 1,3-di(amino)oxyallyl radical cations. When applied to parent vinamidines, this protocol allows for a simple straightforward synthesis of α-keto-β-diimine ligands, for which no convenient synthesis was previously available.Oxidation of vinamidinium salts with meta-chloroperbenzoic acid not only provides access to new persistent 1,3-di(amino)oxyallyl radical cations, but also to α-keto-β-diimine ligands, for which no convenient synthesis was previously available.β-Diketiminates, so-called NacNac ligands (Scheme 1), have been a focus in coordination chemistry for decades.1 Structural modifications include a large variety of N-substituents, as well as bulky,2 electron-withdrawing,3 or electron donating4 R groups. Substitution at the central carbon atom (R′ ≠ H) has also been explored as a strategy to tame this reactive position and enhance the chemical stability of the complex.5 The α-keto-β-diimines are among rare representatives with a more significant modification at the central carbon. These electron-deficient ligands have found applications in the design of highly active nickel(ii) initiators for the synthesis of high molecular weight polyethylenes and poly-α-olefins.6 Interestingly, low-disperse semi-crystalline polymers could be obtained under living conditions and remarkable enantiomorphic site control could be achieved.7Open in a separate windowScheme 1Previously reported synthesis of α-keto-β-diimines and synthesis of air-persistent radical 4˙+ from vinamidinium 3.The low availability of α-keto-β-diimines has clearly hampered further development. Their metal complexes have been known for long, but only as occasional by-products from the air-decomposition of unprotected NacNac complexes (R′ = H).8 To date only a rare selective oxygen-degradation of copper(ii) complexes allows for the synthesis of a handful of 2,4-di(arylimino)pentan-3-ones 2 from the corresponding vinamidines 1.6a,d,9 The procedure requires (i) the synthesis of the NacNac–Cu(ii) complex, (ii) oxidation at the ligand with dioxygen in a methanol/dichloromethane mixture, (iii) the decomplexation and hydrolysis of the resulting hemiacetal ligand (Scheme 1). In turn, we had to synthesize 2,4-bis((2,6-diisopropylphenyl)imino)pentan-3-one 2a and experienced firsthand the length and limitations of this methodology. Among the three steps, the oxidation of the NacNac–copper complex is especially inconvenient and wasteful, as it consists of a continuous bubbling of pure dioxygen in a warm solution for two days.6a Recently, we released a parented, though in principle far simpler, oxidation of tetrakis(dimethylamino) vinamidinium 3 into di(amidinium)ketone 42+ with meta-chloroperbenzoic acid (m-CPBA) as oxidant. Our initial focus was on the corresponding radical 4˙+, which was found remarkably air-persistent, despite minimal steric hindrance.10 Herein we report how further assessment of such 1,3-(diamino)oxyallyl radical cations ultimately led to a straightforward protocole for the synthesis of α-keto-β-diimines from NacNac precursors.Prior to 4˙+, only two oxyallyl radical cations had been synthesized from the reaction of rare stable electrophilic carbenes with carbon monoxide.11–13 In principle, the oxidation of vinamidinium salts should provide for a more simple and general route, with no need of sophisticated N-substituents. To probe this assumption, we first considered the oxidative functionalization of the chloride salt of vinamidinium 5+, which was synthesized from N,N-dimethyl-benzamide and 1-dimethylamino-1-phenylethene.14 Addition of m-CPBA at room temperature yielded 2-chlorovinamidium 6 in 71% yield (Scheme 2). This result indicated the competitive formation of meta-chlorobenzoyl hypochlorite Cl(C6H4)CO2Cl, from the reaction of chloride anions with m-CPBA.15 Therefore we proceeded to an anion metathesis. The resulting tetrafluoroborate salt reacted with m-CPBA, but this time to afford 7·H+, which was fully characterized and isolated in 74% yield. Of note, the NMR spectra of vinamidiniums 6 and 7·H+ mostly differ in the 13C chemical shift of their central carbon: 94 and 127 ppm, respectively. They were unambiguously characterized by mass spectrometry analyses and X-ray diffraction studies (Fig. 1).Open in a separate windowScheme 2Redox transformations of di(imidazole)methane and 1,3-di(phenyl) vinamidinium derivatives.Open in a separate windowFig. 1X-ray structures of 6, 7·H+ and 2c,d with thermal ellipsoids drawn at 50% probability level. Most hydrogen atoms, solvent molecules and counter-anions were omitted for clarity.Solutions of 7·H+ featured an EPR signal upon exposure to air. This slow reaction could be brought to fast completion in presence of potassium hydrogenocarbonate. The remarkable persistency under aerobic conditions of the resulting radical (in aerated solutions for several hours) was reminiscent of our previously reported stable oxyallyl radicals, some being similarly synthesized by auto-oxidation of parented enol-cations.11a Therefore, we hypothesized the formation of radical 7˙+. Although the radical ultimately decayed and couldn''t be isolated, the excellent fit between the experimental EPR hyperfine coupling constants16 and the calculated values17 for 7˙+ strongly supported this reasonable assumption (Fig. 2a). The reaction of 7·H+ with excess meta-chloroperbenzoic acid or stronger oxidants, such dibromine or potassium ferricyanate, led to over oxidation and directly afforded EPR-silent mixtures of trione 8 and the corresponding hydrated gem-diol 8·H2O,18 likely through the formation and subsequent hydrolysis of electron-poor di(iminium)ketone 72+.Open in a separate windowFig. 2Experimental isotropic X-band EPR spectra in dichloromethane at room temperature (plain black line) of 7˙+ (a), 10˙+ (b) and a crude reaction mixture of m-CPBA and 1a (c). Simulated spectra (dashed blue line) were obtained with (a) a Lorentzian line-broadening parameter of 0.22 and the following set of hyperfine constants: a(14N) = 8.6 MHz (2 nuclei) and a(1H) = 12.0 MHz (12 nuclei); (b) with a Lorentzian line-broadening parameter of 0.013 and the following set of hyperfine constants: a(14N) = 3.1 MHz (4 nuclei), a(1H) = 6.5 MHz (12 nuclei) and a(1H) = 0.86 MHz (4 nuclei); (c) with a Lorentzian line-broadening parameter of 0.37 and the following set of hyperfine constants: a(14N) = 7.8 MHz (2 nuclei), a(1H) = 16.5 MHz (1 nucleus) and a(1H) = 15.6 MHz (6 nuclei).We turned to mono(methine)cyanine 9 featuring electron-richer benzimidazole patterns.19 However, the reaction of 9 with m-CPBA afforded known20 1,3-dimethyl- benzimidazolium 10, and not the expected di(benzimidazolium)ketone 132+ (Scheme 2). Note that uncompleted, but clean, formation of 10 was still observed when adding sub-stoichiometric (one equivalent) m-CPBA over one hour at −78 °C. Importantly, dication 132+ could be finally synthesized by the oxidation of di(imine)methane 1119 by m-CPBA, followed by di(alkylation) of the resulting di(imine)ketone 12. Given that 132+ was found almost unreactive towards water, the formation of 10 from 9 results from further oxidative cleavages of 132+, and not its hydrolysis.21 According to cyclic voltammetry experiments, 132+ undergoes successive reductions at E1/2 = −0.12 V vs. Fc/Fc+ (reversible) and Epc = −0.9 V (with further chemical evolution), which we attributed to the formation of radical cation 13˙+ and zwitterionic oxyallyl 13, respectively (see ESI†). We performed the electrochemical reduction of a solution of 132+ in acetonitrile at E = −0.5 V. The stoichiometry (one coulomb per mole of substrate), the observation of a strong EPR signal, as well as an excellent fit between experimental and theoretical hyperfine coupling constants, confirmed the formation of persistent 13˙+ (Fig. 2b), which ultimately decayed at room temperature after several hours.The formation of di(imine)ketone 12 from 11 was so clean that it prompted us to explore further the direct oxidation of NacNac precursors. To our delight, treatment of 1a22 afforded 2a in 98% yield. In contrast with the former long and tedious syntheses from literature, the one-step reaction was completed after one hour at room temperature on multigram scales. EPR monitoring of the reaction showed the formation of a paramagnetic intermediate. Simulation of the hyperfine structure of the spectra required significant coupling with a single proton, in addition to two equivalent nitrogen atoms and six protons (Fig. 2c). This suggested the transient formation of N-protonated radical 1a·H˙+, parented to 4˙+, 7˙+ and 13˙+, thus implying closely related pathways for the m-CPBA oxidation of vinamidiniums and vinamidine 1a.The only few reported β-di(imine)ketones were derivatives of acetylacetone and ortho-substituted anilines. Apart from 1a, which can be stored for several days, they were described as unstable ligands, to be used as soon as synthesized.6d We applied our protocole to vinamidine 1b21 with 2,4,6-trimethylaryl N-substituents and, indeed, the resulting ketone 2b decayed into a complex mixture within hours. Fast work-up allowed for its isolation in 75% yield (Scheme 3). However, even freshly crystalized 2b contained an impurity with similar NMR chemical shifts, except for a 13C NMR signal (quarternary carbon) at 94 ppm in place of the CO band of 2b at 194 ppm. Although the instability of 2b limited further investigations, drying crystals in vacuo in presence of P2O5 decreased the amount of impurity, allowing us to assign this latter to the corresponding hydrated gem-diol 2b·H20.23,24Open in a separate windowScheme 3One-step synthesis of α-keto-β-diimines 2a–d from vinamidines 1a–d.Finally, we considered vinamidines 1c25 and 1d,4b,d with phenyl and di(methyl)amino R groups, respectively. The corresponding di(imine)ketones 2c,d, which are out of reach of previous methods, were isolated in 86–87% yield. They features similar key structural data (IRATR: ν = 1700 cm−1; 13C NMR δCO = 194–191 ppm). Their structures were asserted by a structural X-ray diffraction study (Fig. 1). Importantly, in ketones 2c,d were found remarkably bench stable and have been stored for month with no noticeable degradation.In conclusion, the synthesis and characterization of radicals 7˙+ and 13˙+ are further evidences that introducing 1,3-di(amino)oxyallyl patterns is a robust principle for the design of persistent radical cations. However, the outcome of the reaction of vinamidiniums with m-CPBA is too dependent of the substitution pattern to constitute a general route and over-oxidation is only manageable with extra electron-donating amino groups. In contrast, when applied to vinamidines, this protocol allows for a straightforward synthesis of α-keto-β-diimines. In addition to its simplicity, stable derivatives were isolated, with unprecedented bulky or electron-donating R groups. We are now evaluating these new ligands for nickel-initiated polymerization of ethylene. 相似文献
76.
R N Rai M Kumar A Srivastava R D Joshi A K Asthana V C Tripathi K K Dutta 《The Journal of communicable diseases》1989,21(3):214-217
Twenty-seven cases of Post Kala-Azar Dermal Leishmaniasis (P. K. D. L.) were detected in an endemic focus of Kala-azar in Sujabad village in Varanasi Distt. Male-Female ratio of cases was 4.4:1. Majority (66.6 per cent) of cases had macular lesions. Histopathology of one case showed Leishmania donovani (L. D.) bodies. Densities of sand fly were more in pockets where P. K. D. L. cases were detected. All the 13 cases, which were treated with sodium antimony gluconate, responded well to therapy. 相似文献
77.
78.
C. D. P. Tripathi R. Gupta P. K. Kushawaha C. Mandal S. Misra Bhattacharya A. Dube 《Parasite immunology》2014,36(6):253-265
The immunoprophylactic and therapeutic potentials of root extracts of Withania somnifera chemotypes (NMITLI‐118, NMITLI‐101) and pure withanolide–withaferin A was investigated against Leishmania donovani infection in hamsters. The naive animals, fed orally with immunostimulatory doses of chemotypes 101R, 118R (10 and 3 mg/kg) and withaferin A (9 and 3 mg/kg) for five consecutive days and challenged with Leishmania parasites on day 6, were euthanized on days 30 and 45 p.c. for the assessment of parasite clearance, real‐time analysis of mRNAs of Th1/Th2 cytokines (IFN‐γ, IL‐12, TNF‐α, iNOS/IL‐4, IL‐10 and TGF‐β), NO production, reactive oxygen species (ROS) generation, lymphocyte transformation test and antibody responses. By day 45 p.c., there was a significant increase in the mRNA expression of iNOS, IFN‐γ, IL‐12 and TNF‐α but decrease in IL‐4, IL‐10 and TGF‐β, an enhanced Leishmania‐specific LTT response as well as ROS, NO and antileishmanial IgG2 levels in 101R‐treated hamsters followed by 118R‐ and withaferin A‐treated ones, respectively. When these chemotypes were given to L. donovani‐infected hamsters at different doses, there was moderate therapeutic efficacy of chemotype 101R (~50%) at 30 mg/kg × 5 followed by the other two. The results established that the 101R is the most potential chemotype and can be evaluated for combination therapy along with available antileishmanials. 相似文献
79.
Ashwin K. Panchasara Jayshree C. Patel Vishalkumar K. Vadgama Manish J. Barvaliya C. B. Tripathi 《Journal of anesthesia》2014,28(5):727-732
Purpose
Long-term use of rosuvastatin may be associated with myotoxicity. Statins are one of the groups commonly found to be associated with neuromuscular weakness. The present study was designed to investigate the interaction between rosuvastatin and rocuronium in vivo by using a sciatic-gastrocnemius nerve-muscle preparation of rat.Methods
In our study groups, animals received rosuvastatin 2 mg/kg for 14 and 28 days. Train of four (TOF) stimulation was applied to the sciatic nerve, and gastrocnemius muscle contractions were recorded in Wistar albino rats. Intravenous infusion of rocuronium was given until the twitch responses were abolished. We ultimately compared the effective dose required for a desired effect in 95% of the population (ED95), duration 25 %, deep block, recovery index, and time for returning of TOF ratio to 0.9 between the active control and study groups.Results
Chronic administration of rosuvastatin at a dose of 2 mg/kg for 28 days significantly reduced the ED95 of rocuronium as compared to the active control group. Deep block and duration 25 % were increased by 3.5 and 2.5 times, respectively, compared to the active control group. The spontaneous recovery of neuromuscular block was delayed, as evidenced by the prolonged recovery index and increase in time required for a return of the TOF ratio to 0.9.Conclusion
The neuromuscular blocking potency of rocuronium is increased and recovery is delayed in rats that pre-treated with rosuvastatin. 相似文献80.
The present study investigates the process of internalization for bulk ZnO particles in macrophages, and further elucidates the underlying mechanism. Since macrophages are active phagocytes and phagocytosis is a size dependent phenomenon, therefore we hypothesized that bulk ZnO may internalize into macrophages by phagocytic pathways. Interestingly, the phagocytic activity got enhanced in bulk ZnO treated macrophages. Moreover, the bulk ZnO treated macrophages internalized via FcγR-II/III, complement and scavenger–receptor pathways. To confirm the specificity of phagocytic pathway, the uptake was also analyzed in splenocytes where phagocytic (monocytes) and non-phagocytic cells (lymphocytes) are present. It was observed that no significant uptake of bulk ZnO in case of lymphocytes whereas significant uptake in monocytes. Henceforth, our quest for uptake mechanisms also revealed that severe plasma membrane extensions (pseudopodia), FcγR clustering over the surface of macrophages and activation of FcγR signaling were the key players for bulk ZnO uptake; whereas clathrin or caveolae mediated endocytic pathways contributed less. Uptake of these particles was further strengthened by the ZnO-induced activation of the Src-kinase p-Lyn, phospho-tyrosine kinases Syk (spleen tyrosine kinase), p-PLC-γ and PI3K (phosphatidylinositol 3-kinase). Our findings illustrate that the phagocytic nature of macrophages could have led to higher uptake of bulk ZnO. 相似文献