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991.
Rinner U Hillebrenner HL Adams DR Hudlicky T Pettit GR 《Bioorganic & medicinal chemistry letters》2004,14(11):2911-2915
Structurally modified derivatives of 7-deoxypancratistatin have been synthesized and evaluated in cancer cell line inhibition studies. 相似文献
992.
Parmee ER He J Mastracchio A Edmondson SD Colwell L Eiermann G Feeney WP Habulihaz B He H Kilburn R Leiting B Lyons K Marsilio F Patel RA Petrov A Di Salvo J Wu JK Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2004,14(1):43-46
Substituted 4-amino cyclohexylglycine analogues were evaluated for DP-IV inhibitory properties. Bis-sulfonamide 15e was an extremely potent 2.6 nM inhibitor of the enzyme with excellent selectivity over all counterscreens. 2,4-difluorobenzenesulfonamide 15b and 1-naphthyl amide 16b, however, combined an acceptable in vitro profile with good pharmacokinetic properties in the rat, and 15b was orally efficacious at 3 mpk in an OGTT in lean mice. 相似文献
993.
Hale JJ Doherty G Toth L Li Z Mills SG Hajdu R Ann Keohane C Rosenbach M Milligan J Shei GJ Chrebet G Bergstrom J Card D Rosen H Mandala S 《Bioorganic & medicinal chemistry letters》2004,14(13):3495-3499
3-(N-Alkyl)aminopropylphosphonic acids are potent agonists of four of the five known sphingosine-1-phosphate (S1P) receptor subtypes. 相似文献
994.
Njoroge FG Vibulbhan B Pinto P Strickland C Kirschmeier P Bishop WR Girijavallabhan V 《Bioorganic & medicinal chemistry letters》2004,14(23):5877-5880
Successful efforts to make farnesyl transferase (FT) inhibitors with appropriately tethered ligands designed to interact with a catalytic zinc that exist in the enzyme have been realized. Thus, by introducing either a pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of the piperidine ring, FT inhibitors with activities in the picomolar range have been achieved as exemplified by compounds 12a and 12b. An X-ray structure of 11b bound to FT shows the enhanced activity is a result of interacting with the active-site zinc. 相似文献
995.
Karageorge GN Bertenshaw S Iben L Xu C Sarbin N Gentile A Dubowchik GM 《Bioorganic & medicinal chemistry letters》2004,14(23):5881-5884
A series of tetrahydroisoquinolines has yielded potent MT(2) receptor antagonists, which are selective versus the MT(1) receptor. 相似文献
996.
Antidote-mediated control of an anticoagulant aptamer in vivo 总被引:1,自引:0,他引:1
Rusconi CP Roberts JD Pitoc GA Nimjee SM White RR Quick G Scardino E Fay WP Sullenger BA 《Nature biotechnology》2004,22(11):1423-1428
Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of the drug activity is independent of underlying patient physiology and co-morbidities. Until recently, however, there was no general method to discover antidote-controlled drugs. Here we demonstrate that the activity and side effects of a specific class of drugs, called aptamers, can be controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer, systemically induces anticoagulation in pigs and inhibits thrombosis in murine models. The antidote rapidly reverses anticoagulation engendered by the drug, and prevents drug-induced bleeding in surgically challenged animals. These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals. 相似文献
997.
998.
999.
Kawata T Ito H Uno T Saito M Yamamoto S Furusawa Y Durante M George K Wu H Cucinotta FA 《Cytogenetic and genome research》2004,104(1-4):211-215
Radiation-induced chromosome damage can be measured in interphase using the Premature Chromosome Condensation (PCC) technique. With the introduction of a new PCC technique using the potent phosphatase inhibitor calyculin-A, chromosomes can be condensed within five minutes, and it is now possible to examine the early damage induced by radiation. Using this method, it has been shown that high-LET radiation induces a higher frequency of chromatid breaks and a much higher frequency of isochromatid breaks than low-LET radiation. The kinetics of chromatid break rejoining consists of two exponential components representing a rapid and a slow time constant, which appears to be similar for low- and high-LET radiations. However, after high-LET radiation exposures, the rejoining process for isochromatid breaks influences the repair kinetics of chromatid-type breaks, and this plays an important role in the assessment of chromatid break rejoining in the G2 phase of the cell cycle. 相似文献
1000.
A case of a renal artery stenosis and ipsilateral renal cell carcinoma with long term results is reported. A 65-year-old man with renovascular hypertension, renal insufficiency, and nephrotic range proteinuria presented with an incidental renal cell carcinoma. Concomitant in situ left partial nephrectomy and splenorenal arterial bypass was achieved. The patient is doing well without evidence of malignancy, stable renal function, markedly improved proteinuria and stable blood pressure more than three years later. The techniques of this procedure are detailed and underscore the possibility of successful removal of a renal cell carcinoma with preservation of renal function despite renal artery stenosis. 相似文献