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71.
The purpose of this study was to develop a technique to evaluate the implant-abutment gap of an external hexagon implant system as a function of radius. Six implants of 3.75 mm in diameter (Conexao Sistema de Protese Ltda, Sao Paulo, Brazil) and their respective abutments were screw connected and torqued to 20 N cm(-1). The implants were mounted in epoxy assuring an implant long-axis position perpendicular to the vertical axis. Each implant was grounded through its thickness parallel to implant long-axis at six different distance interval. Implant-abutment gap distances were recorded along the implant-abutment region for each section. Individual measurements were related to their radial position through trigonometric inferences. A sixth degree polynomial line fit approach determined radial adaptation patterns for each implant. Micrographs along implant sections showed a approximately 300 mum length implant-abutment engagement region. All implants presented communication between external and internal regions through connection gaps and inaccurate implant-abutment alignment. Average gap distances were not significantly different between implants (P > 0.086). Polynomial lines showed implant-abutment gap values below 10 mum from 0 mum to approximately 250 mum of the implant-abutment engagement region. Gap distances significantly increased from approximately 250 mum to the outer radius of the implant-abutment engagement region. The technique described provided a broader scenario of the implant-abutment gap adaptation compared with previous work concerning implant-abutment gap determination, and should be considered for better understanding mechanical aspects or biological effects of implant-abutment adaptation on peri-implant tissues. 相似文献
72.
Philipp Y Maximov Russell E McDaniel Daphne J Fernandes Valeriy R Korostyshevskiy Puspanjali Bhatta Thomas E Mürdter David A Flockhart V Craig Jordan 《British journal of pharmacology》2014,171(24):5624-5635
Background and Purpose
Tamoxifen is a prodrug that is metabolically activated by 4-hydroxylation to the potent primary metabolite 4-hydroxytamoxifen (4OHT) or via another primary metabolite N-desmethyltamoxifen (NDMTAM) to a biologically active secondary metabolite endoxifen through a cytochrome P450 2D6 variant system (CYP2D6). To elucidate the mechanism of action of tamoxifen and the importance of endoxifen for its effect, we determined the anti-oestrogenic efficacy of tamoxifen and its metabolites, including endoxifen, at concentrations corresponding to serum levels measured in breast cancer patients with various CYP2D6 genotypes (simulating tamoxifen treatment).Experimental Approach
The biological effects of tamoxifen and its metabolites on cell growth and oestrogen-responsive gene modulation were evaluated in a panel of oestrogen receptor-positive breast cancer cell lines. Actual clinical levels of tamoxifen metabolites in breast cancer patients were used in vitro along with actual levels of oestrogens observed in premenopausal patients taking tamoxifen.Key Results
Tamoxifen and its primary metabolites (4OHT and NDMTAM) only partially inhibited the stimulant effects of oestrogen on cells. The addition of endoxifen at concentrations corresponding to different CYP2D6 genotypes was found to enhance the anti-oestrogenic effect of tamoxifen and its metabolites with an efficacy that correlated with the concentration of endoxifen; at concentrations corresponding to the extensive metabolizer genotype it further inhibited the actions of oestrogen. In contrast, lower concentrations of endoxifen (intermediate and poor metabolizers) had little or no anti-oestrogenic effects.Conclusions and Implications
Endoxifen may be a clinically relevant metabolite in premenopausal patients as it provides additional anti-oestrogenic actions during tamoxifen treatment. 相似文献73.
Yuan Ji Daniel J Schaid Zeruesenay Desta Michiaki Kubo Anthony J Batzler Karen Snyder Taisei Mushiroda Naoyuki Kamatani Evan Ogburn Daniel Hall-Flavin David Flockhart Yusuke Nakamura David A Mrazek Richard M Weinshilboum 《British journal of clinical pharmacology》2014,78(2):373-383
Aims
Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT.Methods
Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects.Results
Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10−9) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10−16), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation.Conclusions
In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors. 相似文献74.
75.
自体外周血造血干细胞和自体骨髓移植治疗急性髓性白血病的临床疗效比较研究 总被引:4,自引:0,他引:4
目的:比较自体外周血干细胞移植(APBSCT)与自体骨髓移植治疗CR1期急性髓性白血病(AML)的临床疗效。方法:用APBSCT治疗AML患者27例,用非净化自体骨髓移植(ABMT)治疗AML患者13例,用净化自体骨髓移植(PABMT)治疗AML患者25例。结果:(1)APBSCT组造血重建校其他两组显著加快;(2)APBSCT组的3年无病生存率(DFS)和复发率(RR)分别为51.%和42.2%,与ABMT组的46.2%、46.7%相当,但与净化ABMT组的72.9%、23.7%相比差异有显著性意义。(3)三组的移植相关死亡率(TRM)差异无显著性意义,死亡的主要原因为感染和内脏出血。结论:APBSCT治疗CR1期AML,其造血重建显著快于ABMT,其疗效与ABMT相当,而显著低于PABMT。 相似文献
76.
Shimazaki C; Wisniewski D; Scheinberg DA; Atzpodien J; Strife A; Gulati S; Fried J; Wisniewolski R; Wang CY; Clarkson BD 《Blood》1988,72(4):1248-1254
The efficacy of immunomagnetic beads to purge human myeloma cells from bone marrow ex vivo was evaluated. The optimal conditions for purging were studied first by using three myeloma cell lines: RPMI-8226, SKO- 007, and SKMM-2. Myeloma cells labeled with the vital fluorescent dye Hoechst 33342 were admixed with normal bone marrow cells, and two monoclonal antibodies reactive with the myeloma cells (PCA-1 and BL-3) were added alone or in combination with the cells. Magnetic beads coated with goat antimouse immunoglobulin G were then added, and the tumor cells to which beads were attached were separated from the mixture with a magnet. The efficacy of tumor cell removal was dependent on the bead-to-tumor ratio; a ratio of more than 500 was optimal in the presence of excess normal marrow cells. The combination of monoclonal antibodies PCA-1 and BL-3 increased the tumor cell removal as compared with either antibody alone. Two cycles of treatment were more effective than one cycle was. Under optimal conditions, 2.3 to 4 logs of tumor cells could be removed from the mixture containing 10% myeloma cells without a significant loss of normal hematopoietic progenitors as measured by CFU-GM, CFU-GEM, and BFU-E. When the efficacy of this procedure was tested on fresh bone marrow from patients with multiple myeloma (MM) by using the combination of PCA-1, BL-3, and J-5, 1.6 to 2.5 logs of tumor cells could be removed by one cycle of treatment, even from marrows containing less than 10% myeloma cells. These observations support the use of monoclonal antibody combinations and immunobeads as a reliable and nontoxic method to eliminate contaminating myeloma cells ex vivo in preparation for autologous bone marrow transplantation in patients with MM. 相似文献
77.
Oxidative metabolism of the human eosinophil 总被引:14,自引:1,他引:14
We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst. 相似文献
78.
Chronic granulocytic leukaemia (CGL) cells which contained a high concentration of unsaturated folate binding protein were incubated in suspension culture for a period of 5 h. Cell samples were periodically assayed for binder and these demonstrated active synthesis which was inhibited by puromycin, cyclo heximide, N-ethylmaleimide, and by incubation at 4 degrees C, but not by actinomycin D. Folate binding activity could also be demonstrated in the culture medium and this increased with the duration of incubation. This release of binder was inhibited by culturing the cells at 4 degrees C and by the addition of N-ethylmaleimide, but not by actinomycin D, puromycin, or cycloheximide. When the pre- and post-culture cell lysates were saturated with tritiated folic acid ([3H]PteGlu) and subjected to chromatography on DEAE-agrarose, approximately half of the bound folate eluted with 0.001 M phosphate buffer at pH 6.0 and the other half eluted with 0.2 M buffer at pH 7.2. The culture medium and plasma from this patient with CGL was well as serum from two normal subjects saturated with [3H]PteGlu and similarly chromatographed contained primarily the acidic binder and much less of the binder eluting with the low molarity buffer. Since a folate binding protein immunochemically similar to the binder in CGL cells has been identified in the serum of non-leukaemic subjects, these experiments suggest that the source of circulating folate binding protein may be the immature granulocyte. 相似文献
79.
6q deletions define distinct clinico-pathologic subsets of non- Hodgkin's lymphoma 总被引:11,自引:1,他引:11
Offit K; Parsa NZ; Gaidano G; Filippa DA; Louie D; Pan D; Jhanwar SC; Dalla- Favera R; Chaganti RS 《Blood》1993,82(7):2157-2162
Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate- grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL. 相似文献
80.