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排序方式: 共有7138条查询结果,搜索用时 31 毫秒
971.
Mielniczuk L DeKemp RA Dennie C Yoshinaga K Burwash IG Bénard F Haddad H Beanlands DS Beanlands RS 《Circulation》2005,111(22):e375-e376
972.
973.
974.
Development of the "Cell Chip": a new in vitro alternative technique for immunotoxicity testing 总被引:2,自引:0,他引:2
Ullerås E Trzaska D Arkusz J Ringerike T Adamczewska V Olszewski M Wyczółkowska J Walczak-Drzewiecka A Al-Nedawi K Nilsson G Białek-Wyrzykowska U Stepnik M Loveren HV Vandebriel RJ Løvik M Rydzyński K Dastych J 《Toxicology》2005,206(2):245-256
Predictive testing of immunotoxicity associated with chemical compounds is complicated and cannot be accomplished with a single test. As most of the existing tests for immunotoxicity employ experimental animals, there is an increasing need for alternative tests in vitro. We have developed a new system for in vitro immunotoxicity testing, which employs changes in cytokine expression observed in vitro as an endpoint indicating potential for perturbation of the immune system in vivo. This system named "fluorescent cell chip" (FCC) is based on a number of genetically modified cell lines that regulate the expression of a transgene coding for fluorescent protein enhanced green fluorescent protein (EGFP) in a similar way as they regulate expression of IL-1beta, IL-2, IL-4, IFN-gamma, IL-10, TNF-alpha, and beta-actin. Morphological and functional features of selected cell lines expressing EGFP under the control of cytokine promotors were compared with maternal cell lines and this comparison showed that critical functional features of the maternal cell lines were preserved in EGFP expressing cells. Two chemicals with known immunotoxic activities, cyclosporine A and potassium tetrachloro-platinate(II), mediated compound-specific pattern of inhibition and activation of reporter gene expression. Thus, the "fluorescent cell chip" has demonstrated potential for application as a predictive screening test for immunomodulatory activities of chemicals. The major advantage of this approach is the possibility to apply this test in high throughput screening of high number of compounds for their well defined biological activity. 相似文献
975.
Histamine H(1) antagonists or "antihistamines" are one of the most prescribed drug families in Western countries. They exert their effect by binding to the histamine H(1) receptor, a receptor belonging to the class of rhodopsin-like G protein-coupled receptors (GPCRs). In this review, the binding of ligands to the human histamine H(1) receptor with respect to site-directed mutagenesis studies and molecular modeling techniques is described. The ligands described include agonists (histamine and histaprodifens), a stereoselective partial agonist (lisuride), and selected inverse agonists (mepyramine, acrivastine and triprolidine). 相似文献
976.
Kruijtzer JA Nijenhuis WA Wanders N Gispen WH Liskamp RM Adan RA 《Journal of medicinal chemistry》2005,48(13):4224-4230
All possible peptoid-peptide hybrids of an MC4 receptor agonist were synthesized and investigated on cells expressing different melanocortin (MC) receptor subtypes and for rat grooming behavior. In general, receptor selectivity remained while affinity and potency were decreased. The length of the functional group of Trp was more important for MC3 and MC5 than for MC4 receptor binding. In general, the potency of the peptoid-peptide hybrids to increase rat excessive grooming behavior correlated well with MC4 receptor pharmacology. 相似文献
977.
Macdonald SJ Cameron R Demaine DA Fenton RJ Foster G Gower D Hamblin JN Hamilton S Hart GJ Hill AP Inglis GG Jin B Jones HT McConnell DB McKimm-Breschkin J Mills G Nguyen V Owens IJ Parry N Shanahan SE Smith D Watson KG Wu WY Tucker SP 《Journal of medicinal chemistry》2005,48(8):2964-2971
The synthesis, antiviral and pharmacokinetic properties of zanamivir (ZMV) dimers 8 and 13 are described. The compounds are highly potent neuraminidase (NA) inhibitors which, along with dimer 3, are being investigated as potential second generation inhaled therapies both for the treatment of influenza and for prophylactic use. They show outstanding activity in a 1 week mouse influenza prophylaxis assay, and compared with ZMV, high concentrations of 8 and 13 are found in rat lung tissue after 1 week. Retention of compounds in rat lung tissue correlated both with molecular weight (excluding 3 and 15) and with a capacity factor K' derived from immobilized artificial membrane (IAM) chromatography (including 3 and 15). Pharmacokinetic parameters for 3, 8 and 13 in rats show the compounds have short to moderate plasma half-lives, low clearances and low volumes of distribution. Dimer 3 shows NA inhibitory activity against N1 viruses including the recent highly pathogenic H5N1 A/Chicken/Vietnam/8/2004. In plaque reduction assays, 3, 8 and 13 show good to outstanding potency against a panel of nine flu A and B virus strains. Consistent with its shorter and more rigid linking group, dimer 8 has been successfully crystallized. 相似文献
978.
Smid P Coolen HK Keizer HG van Hes R de Moes JP den Hartog AP Stork B Plekkenpol RH Niemann LC Stroomer CN Tulp MT van Stuivenberg HH McCreary AC Hesselink MB Herremans AH Kruse CG 《Journal of medicinal chemistry》2005,48(22):6855-6869
A series of novel bicyclic 1-heteroaryl-4-[omega-(1H-indol-3-yl)alkyl]piperazines was synthesized and evaluated on binding to dopamine D(2) receptors and serotonin reuptake sites. This class of compounds proved to be potent in vitro dopamine D(2) receptor antagonists and in addition were highly active as serotonin reuptake inhibitors. Some key representatives showed potent pharmacological in vivo activities after oral dosing in both the antagonism of apomorphine-induced climbing and the potentiation of 5-HTP-induced behavior in mice. On the basis of the preclinical data, 8-{4-[3-(5-fluoro-1H-indol-3-yl)propyl]piperazin-1-yl}-4H-benzo[1,4]oxazin-(R)-2-methyl-3-one (45c, SLV314) was selected for clinical development. In vitro and in vivo studies revealed that 45c has favorable pharmacokinetic properties and a high CNS-plasma ratio. Molecular modeling studies showed that the bifunctional activity of 45c can be explained by its ability to adopt two different conformations fitting either the dopamine D(2) receptor pharmacophore or the serotonin transporter pharmacophore. 相似文献
979.
Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia 总被引:17,自引:5,他引:12
Recently it was shown that, analogous to normal hematopoietic cells, the level of CXC chemokine receptor 4 (CXCR-4) expression on acute myeloid leukemia (AML) cells correlates with stromal cell derived factor-1 alpha (SDF-1)-induced chemotaxis. As we speculated that an anomalous organ distribution of AML cells could affect cell survival and thus result in an altered fraction surviving chemotherapy, we examined a possible correlation between patient prognosis and CXCR-4 expression in AML patients. We found that patients with a high CXCR-4 expression in the CD34(+) subset had a significantly reduced survival and a higher probability of relapse, resulting in a median relapse-free survival (RFS) of only 8.3 months. CXCR-4 expression was significantly higher in fetal liver tyrosine kinase-3 (Flt3)/internal tandem duplication (ITD) AML than in Flt3/wild-type (wt) AML. Covariate analysis indicated that the prognostic significance of Flt3/ITDs with respect to RFS was no more apparent when analyzed in conjunction with the expression of CXCR-4 in the CD34(+) subset, suggesting that the poor prognosis of Flt3/ITD AML might be subordinate to the increased CXCR-4 expression. Using a granulocyte colony-stimulating factor receptor (G-CSF-R)-expressing 32D cell line, we observed that SDF-1/CXCR-4 interaction is required for the survival of myeloid differentiating cells, and it also induces a block in G-CSF-induced myeloid differentiation. These data suggest that the SDF-1/CXCR-4 axis may influence therapy responsiveness and defines unfavorable prognosis in AML. 相似文献
980.
Taal HR van den Hil LC Hofman A van der Heijden AJ Jaddoe VW 《Early human development》2012,88(9):711-716