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71.
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73.
Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier 总被引:6,自引:0,他引:6
Kasten P Vogel J Luginbühl R Niemeyer P Tonak M Lorenz H Helbig L Weiss S Fellenberg J Leo A Simank HG Richter W 《Biomaterials》2005,26(29):5879-5889
Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48 m2/g) were compared with beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA) ceramics (both ca. 0.5 m2/g surface) and demineralized bone matrix (DBM). Before implantation in the back of SCID mice carriers were freshly loaded with 2x10(5) expanded human MSC or loaded with cells and kept under osteogenic conditions for two weeks in vitro. Culture conditions were kept free of xenogenic supplements. Deposits of osteoid at the margins of ceramic pores occurred independent of osteogenic pre-induction, contained human cells, and appeared in 416 MSC/CDHA composites compared to 216 MSC/beta-TCP composites. ALP activity was significantly higher in samples with MSC versus empty controls (p<0.001). Furthermore, ALP was significantly (p<0.05) higher for all ceramics when compared to the DBM matrix. Compared to previous studies, overall bone formation appeared to be reduced possibly due to the strict human protocol. Ectopic bone formation in the novel biomaterial CDHA varied considerably with the cell pool and was at least equal to beta-TCP blocks. 相似文献
74.
Yeo GS Connie Hung CC Rochford J Keogh J Gray J Sivaramakrishnan S O'Rahilly S Farooqi IS 《Nature neuroscience》2004,7(11):1187-1189
An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. This mutation markedly impaired receptor autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system. 相似文献
75.
Johann Kaspar Lieberwirth Pascal Joset Anja Heinze Julia Hentschel Anja Stein Antonella Iannaccone Katharina Steindl Alma Kuechler Rami Abou Jamra 《European journal of human genetics : EJHG》2021,29(5):808
Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.Subject terms: Cardiovascular diseases, Development, Medical genetics, Medical genomics 相似文献
76.
Dissecting natural killer cell activation pathways through analysis of genetic mutations in human and mouse 总被引:2,自引:1,他引:2
Summary: Natural killer (NK) cell cytotoxicity is mediated by multiple germ line-encoded activating receptors that recognize specific ligands expressed by tumor cells and virally infected cells. These activating receptors are opposed by NK inhibitory receptors, which recognize major histocompatibility complex class I molecules on potential targets, raising the threshold for NK cell activation. Once an abnormal cell has been detected, NK cells are the sentinel source of cytolytic mediators, such as granzymes and perforins, as well as interferon-γ, which can polarize the immune response to a T-helper 1 cell type. Activation signals are transmitted by adhesion-dependent pathways, immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathways, DAP10 ITAM-independent pathways, and by signaling through immunoreceptor tyrosine-based switch motifs. These pathways activate downstream signaling partners to trigger NK cell cytotoxicity. Some of these downstream molecules are unique to the various pathways, and some of these molecules are shared. Because of the complexity of signals involved in NK cell–target cell interaction, the generation of mice with targeted mutations in signaling molecules involved in adhesion, activation, or inhibition is essential for a precise dissection of the mechanisms regulating NK cell effector functions. Here we review recent advances in the genetic analysis of the signaling pathways that mediate NK cell killing. 相似文献
77.
da Cunha JP Nakayasu ES Elias MC Pimenta DC Téllez-Iñón MT Rojas F Muñoz MJ Manuel M Almeida IC Schenkman S 《Molecular and biochemical parasitology》2005,140(1):75-86
Histone H1 of most eukaryotes is phosphorylated during the cell cycle progression and seems to play a role in the regulation of chromatin structure, affecting replication and chromosome condensation. In trypanosomatids, histone H1 lacks the globular domain and is shorter when compared with the histone of other eukaryotes. We have previously shown that in Trypanosoma cruzi, the agent of Chagas' disease, histone H1 is phosphorylated and this increases its dissociation from chromatin. Here, we demonstrate using mass spectrometry analysis that T. cruzi histone H1 is only phosphorylated at the serine 12 in the sequence SPKK, a typical cyclin-dependent kinase site. We also found a correlation between the phosphorylation state of histone H1 and the cell cycle. Hydroxyurea and lactacystin, which, respectively, arrest parasites at the G1/S and G2/M stages of the cell cycle, increased the level of histone H1 phosphorylation. Cyclin-dependent kinase-related enzymes TzCRK3, and less intensely the TzCRK1 were able to phosphorylate histone H1 in vitro. Histone H1 dephosphorylation was prevented by treating the parasites with okadaic acid but not with calyculin A. These findings suggest that T. cruzi histone H1 phosphorylation is promoted by cyclin dependent kinases, present during S through G2 phase of the cell cycle, and its dephosphorylation is promoted by specific phosphatases. 相似文献
78.
Shebzukhov YV Koroleva EP Khlgatian SV Lagarkova MA Meshcheryakov AA Lichinitser MR Karbach J Jager E Kuprash DV Nedospasov SA 《Immunology letters》2005,100(1):88-93
Thymidylate synthase (TYMS), the critical enzyme for DNA synthesis and a target for chemotherapy, was recently characterized as an oncogene and a potential target for specific immunotherapy. Here we report TYMS-specific antibody response in a fraction of colon cancer patients. Humoral immune response to TYMS is induced by chemotherapy using TYMS inhibitors, such as 5-fluorouracil (5-FU), and may be associated with tumor burden. Therefore, TYMS may serve as a useful serological biomarker for monitoring the course of disease and treatment in cancer patients. 相似文献
79.
Rademakers R Melquist S Cruts M Theuns J Del-Favero J Poorkaj P Baker M Sleegers K Crook R De Pooter T Bel Kacem S Adamson J Van den Bossche D Van den Broeck M Gass J Corsmit E De Rijk P Thomas N Engelborghs S Heckman M Litvan I Crook J De Deyn PP Dickson D Schellenberg GD Van Broeckhoven C Hutton ML 《Human molecular genetics》2005,14(21):3281-3292
80.
Bioactive glasses for in situ tissue regeneration 总被引:4,自引:0,他引:4
Historically the function of biomaterials has been to replace diseased or damaged tissues. Recent findings show that controlled release of the ionic dissolution products of bioactive glasses results in regeneration of tissues. The mechanism for in situ tissue regeneration involves upregulation of seven families of genes that control the osteoblast cell cycle, mitosis and differentiation. In the presence of critical concentrations of Si and Ca ions, within 48 h osteoblasts that are capable of differentiating into a mature osteocyte phenotype begin to proliferate and regenerate new bone. Osteoblasts that are not in the correct phase of the cell cycle and unable to proceed towards differentiation are switched into apoptosis by the ionic dissolution products. A controlled release of soluble Ca and Si from bioactive glass--resorbable polymer composites leads to vascularised soft tissue regeneration. Gene activation by controlled ion release provides the conceptual basis for molecular design of a third generation of biomaterials optimised for in situ tissue regeneration. 相似文献