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91.
Dijana Jeli 《Molecules (Basel, Switzerland)》2021,26(1)
Amorphous solid dispersion drug delivery systems (ASD DDS) were proved to be efficient for the enhancement of solubility and bioavailability of poorly water-soluble drugs. One of the major keys for successful preparation of ASD is the selection of appropriate excipients, mostly polymers, which have a crucial role in improving drug solubility and its physical stability. Even though, excipients should be chemically inert, there is some evidence that polymers can affect the thermal stability of active pharmaceutical ingredients (API). The thermal stability of a drug is closely related to the shelf-life of pharmaceutical products and therefore it is a matter of high pharmaceutical relevance. An overview of thermal stability of amorphous solids is provided in this paper. Evaluation of thermal stability of amorphous solid dispersion is perceived from the physicochemical perspective, from a kinetic (motions) and thermodynamic (energy) point of view, focusing on activation energy and fragility, as well all other relevant parameters for ASD design, with a glance on computational kinetic analysis of solid-state decomposition. 相似文献
92.
Fakhara Sabir Gbor Katona Edina Pallagi Dorina Gabriella Dob Hussein Akel Dniel Berkesi Zoltn Knya Ildik Cska 《Molecules (Basel, Switzerland)》2021,26(5)
The present study aimed to develop n-propyl gallate (PG)-encapsulated liposomes through a novel direct pouring method using the quality-by-design (QbD) approach. A further aim was to coat liposomes with hyaluronic acid (HA) to improve the stability of the formulation in nasal mucosa. The QbD method was used for the determination of critical quality attributes in the formulation of PG-loaded liposomes coated with HA. The optimized formulation was determined by applying the Box–Behnken design to investigate the effect of composition and process variables on particle size, polydispersity index (PDI), and zeta potential. Physiochemical characterization, in vitro release, and permeability tests, as well as accelerated stability studies, were performed with the optimized liposomal formulation. The optimized formulation resulted in 90 ± 3.6% encapsulation efficiency, 167.9 ± 3.5 nm average hydrodynamic diameter, 0.129 ± 0.002 PDI, and −33.9 ± 4.5 zeta potential. Coated liposomes showed significantly improved properties in 24 h in an in vitro release test (>60%), in vitro permeability measurement (420 μg/cm2) within 60 min, and also in accelerated stability studies compared to uncoated liposomes. A hydrogen-peroxide-scavenging assay showed improved stability of PG-containing liposomes. It can be concluded that the optimization of PG-encapsulated liposomes coated with HA has great potential for targeting several brain diseases. 相似文献
93.
Verification of gamma knife based fractionated radiosurgery with newly developed head-thorax phantom
ObjectivePurpose of the study is to verify the Gamma Knife Extend™ system (ES) based fractionated stereotactic radiosurgery with newly developed head-thorax phantom.MethodsPhantoms are extensively used to measure radiation dose and verify treatment plan in radiotherapy. A human upper body shaped phantom with thorax was designed to simulate fractionated stereotactic radiosurgery using Extend™ system of Gamma Knife. The central component of the phantom aids in performing radiological precision test, dosimetric evaluation and treatment verification. A hollow right circular cylindrical space of diameter 7.0 cm was created at the centre of this component to place various dosimetric devices using suitable adaptors. The phantom is made of poly methyl methacrylate (PMMA), a transparent thermoplastic material. Two sets of disk assemblies were designed to place dosimetric films in (1) horizontal (xy) and (2) vertical (xz) planes. Specific cylindrical adaptors were designed to place thimble ionization chamber inside phantom for point dose recording along xz axis. EBT3 Gafchromic films were used to analyze and map radiation field. The focal precision test was performed using 4 mm collimator shot in phantom to check radiological accuracy of treatment. The phantom head position within the Extend™ frame was estimated using encoded aperture measurement of repositioning check tool (RCT). For treatment verification, the phantom with inserts for film and ion chamber was scanned in reference treatment position using X-ray computed tomography (CT) machine and acquired stereotactic images were transferred into Leksell Gammaplan (LGP). A patient treatment plan with hypo-fractionated regimen was delivered and identical fractions were compared using EBT3 films and in-house MATLAB codes.ResultsRCT measurement showed an overall positional accuracy of 0.265 mm (range 0.223 mm–0.343 mm). Gamma index analysis across fractions exhibited close agreement between LGP and film measured dose with ≥90% (max 93%) pixel pass rate at 1 mm of spatial and 1% of dosimetric tolerances. The focal precision test showed the variation of 0.465 mm between radiological and planned iso-centre.ConclusionsThe study demonstrated the suitability of newly developed head-thorax phantom for dosimetric verification of fractionated stereotactic radiosurgery using Extend™ system of Gamma Knife. 相似文献
94.
Multivalent Inhibitors for Carbohydrate‐Processing Enzymes: Beyond the “Lock‐and‐Key” Concept 下载免费PDF全文
Dr. Sébastien G. Gouin 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(37):11616-11628
During the last decades, tremendous chemical efforts have been dedicated to design monovalent inhibitors of carbohydrate‐processing enzymes, with comparatively few rewards in terms of marketed drugs. Recently, an alternative to the traditional “lock and key” approach has emerged. Multivalency, a widely used strategy for lectin inhibition, has been successfully applied to specific glycosidases and glycosyltransferases. 相似文献
95.
Hualong Song Simon J. Allison Viktor Brabec Hannah E. Bridgewater Jana Kasparkova Hana Kostrhunova Vojtech Novohradsky Roger M. Phillips Jitka Pracharova Nicola J. Rogers Samantha L. Shepherd Peter Scott 《Angewandte Chemie (International ed. in English)》2020,59(34):14677-14685
Monosaccharides are added to the hydrophilic face of a self‐assembled asymmetric FeII metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water‐stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53+/+) with respect to the non‐cancerous ARPE‐19 cell line. While the most selective compound is a glucose‐appended enantiomer, its cellular entry is not mainly glucose transporter‐mediated. Glucose conjugation nevertheless increases nuclear delivery ca 2.5‐fold, and a non‐destructive interaction with DNA is indicated. Addition of the glucose units affects the binding orientation of the metallohelix to naked DNA, but does not substantially alter the overall affinity. In a mouse model, the glucose conjugated compound was far better tolerated, and tumour growth delays for the parent compound (2.6 d) were improved to 4.3 d; performance as good as cisplatin but with the advantage of no weight loss in the subjects. 相似文献
96.
A. B. Madhan Kumar R. Jayakumar K. Panduranga Rao 《Journal of polymer science. Part A, Polymer chemistry》1996,34(14):2915-2924
Polypeptide-based acidic proteinoid containing L -glutamic acid and L -aspartic acid in excess and five other neutral and basic amino acids in minor proportions have been synthesized and found that it forms organized aggregates in an aqueous solution. The proteinoid aggregate has been characterized using 13C-NMR, IR, and fluorescence spectroscopic techniques. The c.m.c. of the proteinoid has been determined by conductometric and pH metric methods. The aggregation studies were carried out at different temperatures and varying ionic strengths of the medium. The phase transition of the proteinoid aggregate has been determined using the fluorescence absorbance method. The aggregation behavior is shown to be dependent on the pH of the solution. This was also supported by conductivity measurements. Using methylene blue as a model drug, the drug delivery property of the proteinoid micelles were studied in acidic (pH 4.5) and neutral (pH 7.4) mediums. Using biphasic model thermochemical parameters, ΔG, ΔH, ΔS, and ΔCp have been evaluated. © 1996 John Wiley & Sons, Inc. 相似文献
97.
98.
Poor water solubility and low bioavailability of hydrophobic flavonoids such as rutin remain as substantial challenges to their oral delivery via functional foods. In this study, the effect of pH and the addition of a protein (sodium caseinate; NaCas) on the aqueous solubility and stability of rutin was studied, from which an efficient delivery system for the incorporation of rutin into functional food products was developed. The aqueous solubility, chemical stability, crystallinity, and morphology of rutin (0.1–5% w/v) under various pH (1–11) and protein concentrations (0.2–8% w/v) were studied. To manufacture the concentrated colloidally stable rutin–NaCas particles, rutin was dissolved and deprotonated in a NaCas solution at alkaline pH before its subsequent neutralisation at pH 7. The excess water was removed using ultrafiltration to improve the loading capacity. Rutin showed the highest solubility at pH 11, while the addition of NaCas resulted in the improvement of both solubility and chemical stability. Critically, to achieve particles with colloidal stability, the NaCas:rutin ratio (w/w) had to be greater than 2.5 and 40 respectively for the lowest (0.2% w/v) and highest (4 to 8% w/v) concentrations of NaCas. The rutin–NaCas particles in the concentrated formulations were physically stable, with a size in the range of 185 to 230 nm and zeta potential of −36.8 to −38.1 mV, depending on the NaCas:rutin ratio. Encapsulation efficiency and loading capacity of rutin in different systems were 76% to 83% and 2% to 22%, respectively. The concentrated formulation containing 5% w/v NaCas and 2% w/v rutin was chosen as the most efficient delivery system due to the ideal protein:flavonoid ratio (2.5:1), which resulted in the highest loading capacity (22%). Taken together, the findings show that the delivery system developed in this study can be a promising method for the incorporation of a high concentration of hydrophobic flavonoids such as rutin into functional foods. 相似文献
99.
Drug repurposing is an emerging strategy, which uses already approved drugs for new medical indications. One such drug is gemcitabine, an anticancer drug that only works at high doses since a portion is deactivated in the serum, which causes toxicity. In this review, two methods were discussed that could improve the anticancer effect of gemcitabine. The first is a chemical modification by conjugation with cell-penetrating peptides, namely penetratin, pVEC, and different kinds of CPP6, which mostly all showed an increased anticancer effect. The other method is combining gemcitabine with repurposed drugs, namely itraconazole, which also showed great cancer cell inhibition growth. Besides these two strategies, physiologically based pharmacokinetic models (PBPK models) are also the key for predicting drug distribution based on physiological data, which is very important for personalized medicine, so that the correct drug and dosage regimen can be administered according to each patient’s physiology. Taking all of this into consideration, it is believed that gemcitabine can be repurposed to have better anticancer effects. 相似文献
100.
Shujing Xu Dang Ding Xujie Zhang Lin Sun Dongwei Kang Boshi Huang Xinyong Liu Peng Zhan 《Molecules (Basel, Switzerland)》2022,27(3)
Viral infections pose a persistent threat to human health. The relentless epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health problem, with millions of infections and fatalities so far. Traditional approaches such as random screening and optimization of lead compounds by organic synthesis have become extremely resource- and time-consuming. Various modern innovative methods or integrated paradigms are now being applied to drug discovery for significant resistance in order to simplify the drug process. This review provides an overview of newly emerging antiviral strategies, including proteolysis targeting chimera (PROTAC), ribonuclease targeting chimera (RIBOTAC), targeted covalent inhibitors, topology-matching design and antiviral drug delivery system. This article is dedicated to Prof. Dr. Erik De Clercq, an internationally renowned expert in the antiviral drug research field, on the occasion of his 80th anniversary. 相似文献