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81.
Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan 下载免费PDF全文
Shoji Kubo Yasuni Nakanuma Shigekazu Takemura Chikaharu Sakata Yorihisa Urata Akinori Nozawa Takayoshi Nishioka Masahiko Kinoshita Genya Hamano Hiroaki Terajima Gorou Tachiyama Yuji Matsumura Terumasa Yamada Hiromu Tanaka Shoji Nakamori Akira Arimoto Norifumi Kawada Masahiro Fujikawa Hiromitsu Fujishima Yasuhiko Sugawara Shogo Tanaka Hideyoshi Toyokawa Yuko Kuwae Masahiko Ohsawa Shinichiro Uehara Kyoko Kogawa Sato Tomoshige Hayashi Ginji Endo 《Journal of hepato-biliary-pancreatic sciences》2014,21(7):479-488
82.
Background A solvent/detergent (S/D) treatment in a medical device has been developed for pathogen reduction of plasma for transfusion. Impact of S/D on bacterial growth and on the capacity of complement to kill bacteria has been investigated in this study. Study design and methods A pool of apheresis plasma from four donors was spiked with eight transfusion‐relevant bacteria. Plasma was treated with 1% tri(n‐butyl) phosphate and 1% Triton X‐45 at 31°C for 90 min and then extracted by oil at 31°C for 70 min. Decomplemented plasma and Phosphate Buffer Saline were used as controls. Bacterial count was determined in samples taken immediately after spiking, or after S/D and oil treatment. Similar experiments were conducted using three individual recovered plasma donations. Bacteria growth inhibition tests were performed using discs soaked with plasma samples whether containing the S/D agents or not. Results The mean reduction factors of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae due to complement during S/D treatment were >8·75, 4·71, and 4·18 log in pooled plasma and >7·42, 2·24 and >6·08 log in individual plasmas, respectively. Bacillus cereus and Bacillus subtilis were inactivated by S/D (>7·04 and 1·60 log in pooled, and >6·06 and 2·39 in individual plasmas, respectively). Staphylococcus aureus, Staphylococcus epidermidis and Enterobacter cloacae did not multiply during S/D treatment of plasma. Growth inhibition tests revealed an inhibition of three Gram‐negative bacteria by complement and all Gram‐positive by S/D. Conclusion The S/D treatment of plasma does not alter the bactericidal activity of complement, and inactivates some Gram‐positive bacteria. 相似文献
83.
84.
Locating functionally important protein surfaces and identifying the catalytic site residues are critical for studying enzyme
functions. Here, we present a method for predicting and characterizing catalytic sites of enzymes that is fold-independent.
By extract atomic patterns of catalytic residues in surface pockets computed geometrically, we develop a library of atomic
patterns on protein functional surfaces of ca 700 structures. Together with propensities of secondary structures and residue occurrence in active sites, we develop a method
to identify functionally important surfaces on protein structures and to locate key residues. We discuss application of our
methods to amylase, dioxygenase, deaminase, dehalogenase, and hydratase. A large scale cross-validated prediction study shows
that our method is sensitive and specific. Our method can used to study enzyme function, drug design, and engineering novel
biochemical function. 相似文献
85.
Stewart AK Kurschat CE Alper SL 《Pflügers Archiv : European journal of physiology》2007,454(3):373-384
The ubiquitous AE2/SLC4A2 anion exchanger is acutely and independently regulated by intracellular (pHi) and extracellular pH (pHo), whereas the closely related AE1/SLC4A1 of the red cell and renal intercalated cell is relatively pH-insensitive. We have
investigated the contribution of nonconserved charged residues within the C-terminal transmembrane domain (TMD) of AE2 to
regulation by pH through mutation to the corresponding AE1 residues. AE2-mediated Cl−/Cl− exchange was measured as 4,4′-di-isothiocyanatostilbene-2,2′-disulfonic acid-sensitive 36Cl− efflux from Xenopus oocytes by varying pHi at constant pHo, and by varying pHo at near-constant pHi. All mutations of nonconserved charged residues of the AE2 TMD yielded functional protein, but mutations of some conserved
charged residues (R789E, R1056A, R1134C) reduced or abolished function. Individual mutation of AE2 TMD residues R921, F922,
P1077, and R1107 exhibited reduced pHi sensitivity compared to wt AE2, whereas TMD mutants K1153R, R1155K, R1202L displayed enhanced sensitivity to acidic pHi. In addition, pHo sensitivity was significantly acid- shifted when nonconserved AE2 TMD residues E981, K982, and D1075 were individually converted
to the corresponding AE1 residues. These results demonstrate that multiple conserved charged residues are important for basal
transport function of AE2 and that certain nonconserved charged residues of the AE2 TMD are essential for wild-type regulation
of anion exchange by pHi and pHo.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
A. K. Stewart and C. E. Kurschat have contributed equally to this work. 相似文献
86.
High throughput ranking of recombinant avian scFv antibody fragments from crude lysates using the Biacore A100 总被引:1,自引:0,他引:1
Leonard P Säfsten P Hearty S McDonnell B Finlay W O'Kennedy R 《Journal of immunological methods》2007,323(2):172-179
Advances in molecular evolution strategies have made it possible to identify antibodies with exquisite specificities and also to fine-tune their biophysical properties for practically any specified application. Depending on the desired function, antibody/antigen interactions can be long-lived or short-lived and, therefore, particular attention is needed when seeking to identify antibodies with specific reaction-rate and affinity properties. Surface plasmon resonance (SPR) biosensors routinely generate sensitive and reliable kinetic data from antibody/antigen interactions for both therapeutic and diagnostic applications. However, many kinetic-based screening assays require rigorous sample preparation and purification prior to analysis. To ameliorate this problem, we developed a rapid and reliable assay for characterising recombinant scFv antibody fragments, directly from crude bacterial lysates. Ninety-six scFv antibodies derived from chickens immunised with C-reactive protein (CRP) were selected by phage display and evaluated using the Biacore A100 protein interaction array system. Antibodies were captured from crude bacterial extracts on the sensor chip surface and ranked based on the percentage of the complex left (% left) after dissociation in buffer. Kinetic rate constants (k(a) and k(d)) and affinity (K(D)) data were obtained for six clones that bound monomeric CRP across a broad affinity range (2.54 x 10(-8) to 3.53 x 10(-10) M). Using this assay format the A100 biosensor yielded high quality kinetic data, permitting the screening of nearly 400 antibody clones per day. 相似文献
87.
Tereza Zelenková Maria Julia Mora Antonello A. Barresi Gladys Ester Granero Davide Fissore 《Journal of pharmaceutical sciences》2018,107(4):1157-1166
This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in a confined impinging jet reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, for example, polycaprolactone, is required to support chitosan to obtain a monomodal particle size distribution, with low particle diameters. A surfactant is required to reduce the nanoparticle size (down to a mean diameter of about 260 nm) and obtain a positive zeta potential (about +31 mV), perfectly suitable for pharmaceutical applications. Different surfactants were tested, and Poloxamer 388 appeared to be preferable to polyvinyl alcohol. The effect of the concentration of Poloxamer 388 (in the range 0.5-5 mg mL?1) and of chitosan (in the range 1.5-5 mg mL?1) on both the mean particle size and zeta potential was also investigated, evidencing that chitosan concentration has the strongest effect on both parameters. Finally, the effect of solvent evaporation, quenching and feed flow rate was investigated, showing that the evaporation stage does not affect particle characteristics, quenching is required to avoid particle aggregation, and a minimum liquid flow rate of 80 mL min?1 is required in the considered reactor to minimize the particle size. 相似文献
88.
Tausif Alam Saba Khan Bharti Gaba Md. Faheem Haider Sanjula Baboota Javed Ali 《Journal of pharmaceutical sciences》2018,107(11):2914-2926
The present study demonstrated the systematic adaptation of quality by design-integrated approach for the development of novel nanostructured lipid carrier (NLC) of an anti-hypertensive drug isradipine (ISD) to address the inherent challenges such as low solubility and low oral bioavailability. Plackett-Burman design was used for preliminary screening of significant process and formulation variables (p <0.05), which were further processed using Box-Behnken design for the attainment of optimization goal that is, mean particle size (85.7 ± 7.3 nm), drug entrapment efficiency (87.4 ± 3.29%), and in vitro drug release characteristics (92.89 ± 5.47%). The optimized ISD-NLC formulation also demonstrated well-dispersed uniform-shaped particles (polydispersity index 0.207 ± 0.029), high gastrointestinal fluid stability (zeta potential ?10.17 ± 0.59 mV), and higher in vitro gut permeation (21.69 ± 2.38 μg/cm2 of ISD-NLC as compared to 11.23 ± 1.74 μg/cm2 in ISD suspension). Furthermore, lipolysis studies were performed for the purpose of in vivo fate, and significantly higher drug content of ISD from ISD-NLC in aqueous phase was found (72.34 ± 4.62%) as compared to drug suspension (3.01 ± 0.91%). Relative bioavailability of ISD-NLC and ISD suspension was increased by 4.2-fold and 1.78-fold in the absence and presence of cycloheximide which is a lymphatic uptake inhibitor revealing lymphatic uptake of ISD-NLC in bioavailability improvement. Hence, systematic adaptation of quality by design integrated approach improved gut permeation and potential solubilizaton fate (dynamic lipolysis) of ISD-NLC, which further improved the lymphatic uptake and biodistribution of drug thereby promisingits in vivo prospect and clinical efficacy. 相似文献
89.
蝙蝠葛碱复合纳米胶束的制备及大鼠体内药动学研究 总被引:1,自引:0,他引:1
目的使用聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物(Soluplus~?)和D-α-维生素E聚乙二醇琥珀酸酯(TPGS)作为载体材料制备蝙蝠葛碱复合纳米胶束(dauricine composite nanomicelles,Dau-CNMs),并通过大鼠ig给药评价其药动学情况。方法采用溶剂蒸发-薄膜分散法制备Dau-CNMs,通过单因素实验筛选了Dau-CNMs处方中Soluplus~?与TPGS用量配比;分别考察了Dau-CNMs和蝙蝠葛碱单纯纳米胶束(dauricine single nanomicelles,Dau-SNMs)的微观形态、粒径分布、Zeta电位等理化性质;并通过MTT法评估了Dau-CNMs的细胞毒性,采用Caco-2细胞单层模型评价了蝙蝠葛碱原料药、Dau-SNMs和Dau-CNMs的细胞跨膜转运性质;通过大鼠ig给药比较蝙蝠葛碱混悬液、Dau-SNMs和Dau-CNMs的体内药动学特征。结果经实验筛选得到Dau-CNMs的最优处方:Soluplus~?与TPGS用量比为7∶1;在透射电子显微镜下可观察到Dau-SNMs和Dau-CNMs均呈圆整球状分布;Dau-CNMs的细胞毒性较低,且能够有效提高药物的跨膜转运能力;与蝙蝠葛碱混悬液组和Dau-SNMs组比较,Dau-CNMs组大鼠ig给药显著提高了药物达峰浓度和口服生物利用度。结论以Soluplus~?与TPGS作为载体材料,将蝙蝠葛碱制备成复合纳米胶束,能够显著增加药物生物利用度。 相似文献
90.
目的制备欧前胡素固体分散体,并考察其体内药动学。方法溶剂挥发法制备固体分散体后,检测欧前胡素存在状态,并测定溶解度、溶出率、累积溶出度。大鼠随机分为2组,分别灌胃给予欧前胡素及其固体分散体0??3%CMC?Na混悬液(25 mg/kg),于0.25、0.5、1、1.5、2、3、4、6、8、12 h采血,HPLC法测定欧前胡素血药浓度,计算主要药动学参数。结果欧前胡素以结晶型状态存在,制成固体分散体后转变为无定型状态,溶解度、溶出率、累积溶出度明显升高。与原料药比较,固体分散体tmax缩短(P<0.05),Cmax、AUC0-t、AUC0-∞升高(P<0.01),相对生物利用度增加至2??03倍。结论固体分散体可改善欧前胡素溶解度、溶出率、累积溶出度,促进其体内吸收。 相似文献