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71.
72.
Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers
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Alberto Dal Corso Dr. Michele Caruso Dr. Laura Belvisi Dr. Daniela Arosio Prof. Dr. Umberto Piarulli Dr. Clara Albanese Dr. Fabio Gasparri Dr. Aurelio Marsiglio Dr. Francesco Sola Dr. Sonia Troiani Dr. Barbara Valsasina Dr. Luca Pignataro Dr. Daniele Donati Prof. Dr. Cesare Gennari 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(18):6921-6929
Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the αvβ3‐integrin ligand cyclo[DKP–RGD]‐CH2NH2 ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified αVβ3‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (αVβ3?) and its subclone CCRF‐CEM αVβ3 (αVβ3+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM αVβ3 versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload. 相似文献
73.
Size controlled synthesis of ornithine‐based polypeptides by ring‐opening polymerization of α‐(amino acid)‐N‐carboxyanhydrides
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74.
《Operations Research Letters》2019,47(3):197-201
The Traveling Salesman Problem with Pickup and Delivery seeks a minimum cost path with pickups preceding deliveries. It is important in on-demand last-mile logistics, such as ride sharing and meal delivery. We examine the use of low-width Decision Diagrams in a branch-and-bound with and without Assignment Problem inference duals as a primal heuristic for finding good solutions within strict time budgets. We show these diagrams can be more effective than similarly structured hybrid Constraint Programming techniques for real-time decision making. 相似文献
75.
Dr. Bing Zhang Qilin Yu Prof. Yu Liu 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(60):13698-13703
Graphene oxide (GO)-grafted nanosupramolecules have recently emerged as neoteric nano drug carriers in the therapy of refractory diseases. Herein, a multicomponent nanosupramolecular drug carrier based on a targeted peptide and magnetic GO is reported, the drug-release behavior of which can be regulated by an alternating magnetic field (AMF). This multicomponent nanosupramolecular carrier is composed of β-cyclodextrin (β-CD)/nickel nanoparticle-modified graphene oxide (GONiCD) and mitochondrial ion-targeting peptide (MitP)-grafted hyaluronic acid (HAMitP). Owing to the host–guest interaction between β-cyclodextrin and the cyclohexyl groups on MitP, GONiCD and HAMitP could form supramolecular assemblies during the doxorubicin (Dox) loading process, which not only remarkably enhances the drug-loading capacity, but also improves the drug-release efficiency under AMF stimulus. During co-incubation with tumor cells, the Dox-loaded assemblies could strongly target the tumor mitochondria and damage both the mitochondria and the nuclei, owing to Dox release from the assemblies induced by AMF. This study sheds light on the exploration of peptide caps for controlled drug loading/release of supramolecular nanocarriers for efficient drug delivery and anticancer therapy. 相似文献
76.
《Mendeleev Communications》2020,30(1):25-27
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77.
Multidrug‐Containing,Salt‐Based,Injectable Supramolecular Gels for Self‐Delivery,Cell Imaging and Other Materials Applications
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Rajdip Roy Prof. Parthasarathi Dastidar 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(42):14929-14939
Both molecular and crystal‐engineering approaches were exploited to synthesize a new class of multidrug‐containing supramolecular gelators. A well‐known nonsteroidal anti‐inflammatory drug, namely, indomethacin, was conjugated with six different l ‐amino acids to generate the corresponding peptides having free carboxylic acid functionality, which reacted further with an antiviral drug, namely, amantadine, a primary amine, in 1:1 ratio to yield six primary ammonium monocarboxylate salts. Half of the synthesized salts showed gelation ability that included hydrogelation, organogelation and ambidextrous gelation. The gels were characterized by table‐top and dynamic rheology and different microscopic techniques. Further insights into the gelation mechanism were obtained by temperature‐dependent 1H NMR spectroscopy, FTIR spectroscopy, photoluminescence and dynamic light scattering. Single‐crystal X‐ray diffraction studies on two gelator salts revealed the presence of 2D hydrogen‐bonded networks. One such ambidextrous gelator (capable of gelling both pure water and methyl salicylate, which are important solvents for biological applications) was promising in both mechanical (rheoreversible and injectable) and biological (self‐delivery) applications for future multidrug‐containing injectable delivery vehicles. 相似文献
78.
79.
80.
In a Carsharing System, a fleet of cars is distributed at specified stations in an urban area, users can take and return cars at any time and station. For operating such a system in a satisfactory way, the stations have to keep a good ratio between the total number of places and the number of cars in each station, in order to refuse as few customer requests as possible. In this work, we propose to model the resulting problem of balancing the load of the stations as a General Pickup and Delivery Problem. As problems of this type are known to be hard, we discuss possible heuristic approaches both for the static (offline) and the dynamic (online) version of the problem, and give approximation results for special cases. 相似文献