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991.
Scott Saxman Patrick J. Loehrer Sr. Keith Logie Doyle Stephens Frank Workman Daniel Scullin Lawrence H. Einhorn Rafat Ansari 《Investigational new drugs》1991,9(3):253-256
Forty-six previously untreated patients with advanced non-small cell lung cancer (NSCLC) were entered into a Hoosier Oncology Group phase II trial of daily oral etoposide 50 mg/m2/d. The dose limiting toxicity was granulocytopenia. The non-hematologic toxicity was mild, with only 19% of patients developing Grade 3 or 4 leukopenia. Two partial responses of 10 and 16 weeks duration were seen in 43 evaluable patients, for an overall response rate of 4%. We conclude that daily oral etoposide has minimal activity in advanced NSCLC, and does not improve response rates over conventional 1–5 day intravenous etoposide administration.from the Hoosier Oncology Group, the Walther Cancer Institute, Indianapolis, IN; Department of Medicine, Indiana University, Indianapolis, IN, USADr. Einhorn is the Walther American Cancer Society Professor of Clinical Oncology. 相似文献
992.
993.
Lea L. Sorret Connor R. Monticello Madison A. DeWinter Daniel K. Schwartz Theodore W. Randolph 《Journal of pharmaceutical sciences》2019,108(1):162-172
Silicone oil, used as a lubricating coating in pharmaceutical containers, has been implicated as a cause of therapeutic protein aggregation. After adsorbing to silicone oil-water interfaces, proteins may form interfacial gels, which can be transported into solution as insoluble aggregates if the interfaces are perturbed. Mechanical interfacial perturbation of both monomeric recombinant human interleukin-1 receptor antagonist (rhIL-1ra) and PEGylated rhIL-1ra (PEG rhIL-1ra) in siliconized syringes resulted in losses of soluble monomeric protein. However, the loss of rhIL-1ra was twice that for PEG rhIL-1ra; even though in solution, PEG rhIL-1ra had a lower ΔGunf and exhibited a more perturbed tertiary structure at the interface. Net protein-protein interactions in solution for rhIL-1ra were attractive but increased steric repulsion because of PEGylation led to net repulsive interactions for PEG rhIL-1ra. Attractive interactions for rhIL-1ra were associated with increases in intermolecular β-sheet content at the interface, whereas no intermolecular β-sheet structures were observed for adsorbed PEG rhIL-1ra. rhIL-1ra formed interfacial gels that were 5 times stronger than those formed by PEG rhIL-1ra. Thus, the steric repulsion contributed by the PEGylation resulted in decreased interfacial gelation and in the reduction of aggregation, in spite of the destabilizing effects of PEGylation on the protein’s conformational stability. 相似文献
994.
Sreekanth Thota Srujana Vallala Rajeshwar Yerra Daniel Alencar Rodrigues Eliezer J. Barreiro 《Medicinal chemistry research》2016,25(10):2127-2132
The synthesis and characterization of ruthenium complexes (Ru-1–Ru-6) of the type [Ru(R)2(K)]2+ (where R?=?1,10-phenanthroline/2,2′-bipyridyl and K?=?acetyl coumarin-inh, pyrazole-tch, acetyl coumarin-tsz, are described. These ligands form bidentate octahedral ruthenium complexes. The in vitro cytotoxic activities of the complexes measurement against the human cancer T-lymphocyte cell lines. In vitro evaluation of these title complexes revealed cytotoxicity from 0.34 to 1.4?µg/mL against CEM, 0.28 to 1.8?µg/mL against L1210, 0.44 to 2.5?µg/mL against Molt4/C8, 0.98 to 1.6?µg/mL against HL60, and 0.66 to 1.4?µg/mL against BEL7402. Ruthenium complexes Ru-5 & Ru-6 showed that quite significant anticancer activities over standard drugs. 相似文献
995.
Chen L Gao G Felczak K Bonnac L Patterson SE Wilson D Bennett EM Jayaram HN Hedstrom L Pankiewicz KW 《Journal of medicinal chemistry》2007,50(23):5743-5751
Novel tiazofurin adenine dinucleotide (TAD) analogues 25-33 containing a substituent at C2 of the adenine ring have been synthesized as inhibitors of the two isoforms of human IMP-dehydrogenase. The 2-ethyl TAD analogue 33 [Ki = 1 nM (type I), Ki = 14 nM (type II)] was found to be the most potent. It did not inhibit three other cellular dehydrogenases up to 50 microM. Mycophenolic adenine bis(phosphonate)s containing a 2-phenyl (37) or 2-ethyl group (38), were prepared as metabolically stable compounds, both nanomolar inhibitors. Compound 38 [Ki = 16 nM (type I), Ki = 38 nM (type II)] inhibited proliferation of leukemic K562 cells (IC50 = 1.1 microM) more potently than tiazofurin (IC50 = 12.4 microM) or mycophenolic acid (IC50 = 7.7 microM). 相似文献
996.
997.
Glujovsky Demian Sueldo Carlos E. Bardach Ariel del Pilar Valanzasca María Comandé Daniel Ciapponi Agustín 《Journal of assisted reproduction and genetics》2020,37(2):263-268
Journal of Assisted Reproduction and Genetics - To evaluate if the authors of published systematic reviews (SRs) reported the level of quality of evidence (QoE) in the top 5 impact factor... 相似文献
998.
A phase 1 study of the CXCR4 antagonist plerixafor in combination with high‐dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators’ Consortium study (POE 10‐03) 下载免费PDF全文
999.
1000.
Karrout Y Neut C Siepmann F Wils D Ravaux P Deremaux L Flament MP Dubreuil L Lemdani M Desreumaux P Siepmann J 《The Journal of pharmacy and pharmacology》2010,62(12):1676-1684
Objectives Film coatings based on blends of Eurylon 6 HP‐PG (a hydroxypropylated and pregelatinized high amylose starch) and ethylcellulose were to be evaluated as promising coating materials for site‐specific drug delivery to the colon of patients suffering from inflammatory bowel diseases. Methods Pellet starter cores containing 60% 5‐aminosalicylic acid were prepared by extrusion/spheronization and coated with different Eurylon 6 HP‐PG : ethylcellulose blends at various coating levels. Drug release was measured in media simulating the contents of the upper gastrointestinal tract (in the presence and absence of enzymes) as well as in media simulating the contents of the colon. Key findings 5‐Aminosalicylic acid release could effectively be suppressed in 0.1 N HCl and phosphate buffer pH 6.8, optionally containing pepsin or pancreatin, but occurred as soon as the pellets came into contact with culture medium inoculated with faecal samples from inflammatory bowel disease patients. This can be attributed to the partial degradation of the starch derivative by enzymes secreted by bacteria present in the colon of these patients. Conclusions The presented drug delivery system is adapted to the pathophysiological conditions in inflammatory bowel disease patients. Furthermore, drug release remained unaltered upon 1 year open storage. 相似文献