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31.
Molyneux G Gibson FM Gordon-Smith EC Pilling AM Liu KC Rizzo S Sulsh S Turton JA 《International journal of experimental pathology》2005,86(6):415-430
Mitomycin (MMC), like many antineoplastic drugs, induces a predictable, dose-related, bone marrow depression in man and laboratory animals; this change is generally reversible. However, there is evidence that MMC may also cause a late-stage or residual bone marrow injury. The present study in female CD-1 mice investigated the haematological and bone marrow changes induced by MMC in a repeat dose study lasting 50 days. Control and MMC-treated mice were dosed intraperitoneally on eight occasions over 18 days with vehicle, or MMC at 2.5 mg/kg, autopsied (n = 6-12) at 1, 7, 14, 28, 42 and 50 days after the final dose and haematological changes investigated. Femoral nucleated bone marrow cell counts and levels of apoptosis were also evaluated and clonogenic assays carried out; serum levels of FLT3 ligand (FL) were assessed. At day 1 post-dosing, MMC induced significant reductions in RBC, Hb and haematocrit (HCT) values, and there were decreases in reticulocyte, platelet, and femoral nucleated cell counts (FNCC); neutrophil, lymphocyte and monocyte values were also significantly reduced. On days 7 and 14 post-dosing, all haematological parameters showed evidence of a return towards normal values, but at these times, and at day 28, values for RBC and FNCC remained significantly reduced in comparison with controls. At days 42 and 50 post-dosing, many haematological parameters in MMC-treated mice had returned to control levels; however, there remained evidence of late-stage effects on RBC, Hb and HCT values, and FNCC also continued to be significantly decreased. Results for granulocyte-macrophage colony-forming units and erythroid colonies showed a profound decrease immediately post-dosing, but a return to normal values was evident at day 50. Serum FL concentrations demonstrated very significant increases in the immediate post-dosing period, but a return to normal was seen at day 50 post-dosing; a relatively similar pattern was seen in the number of apoptotic femoral marrow nucleated cells. The histopathological examination of kidney tissues from MMC animals at day 42 and 50 post-dosing showed evidence of hydronephrosis with cortical glomerular/tubular atrophy and degeneration. It is therefore concluded that MMC administered on eight occasions over 18 days to female CD-1 mice at 2.5 mg/kg induced profound changes in haematological and bone marrow parameters in the immediate post-dosing period with a return to normal levels at day 50 post-dosing; however, there was evidence of mild but significant late-stage/residual effects on RBC and FNCC, and on cells of the erythroid lineage in the bone marrow. 相似文献
32.
Chuen -Mao Yang Hui -Liang Tsao Chi -Tso Chiu Lir -Wan Fan Sheu -Meei Yu 《Pflügers Archiv : European journal of physiology》1996,432(4):708-716
The effects of increases in cellular adenosine 3′5′-cyclic monophosphate (cAMP) on 5-hydroxytryptamine-(5-HT-) induced generation
of inositol phosphates (IPs) and increases in intracellular Ca2+ ([Ca2+]i) were investigated using canine cultured tracheal smooth muscle cells (TSMCs). Cholera toxin and forskolin induced concentration-
and time-dependent cAMP formation with half-maximal effects (−logEC50) produced at concentrations of 7.0 ± 0.5 and 4.9 ± 0.4 respectively. Pretreatment of TSMCs with either forskolin or dibutyryl
cAMP inhibited 5-HT-stimulated responses. Even after treatment for 24h, these agents still inhibited the 5-HT-induced Ca2+ mobilization. The inhibitory effects of these agents produced both depression of the maximal response and a shift to the
right of the concentration response curves of 5-HT. The water-soluble forskolin analogue L-858051 [7-deacetyl-7β-(γ-N-methylpiperazino)-butyryl forskolin] significantly inhibited the 5-HT-stimulated accumulation of IPs. In contrast, the addition
of 1,9-dideoxy forskolin, an inactive forskolin analogue, had little effect on this response. Moreover, SQ-22536 [9-(tetrahydro-2-furanyl)-9-H-purin-6-amine], an inhibitor of adenylate cyclase, and both H-89 [N-(2-aminoethyl)-5-isoquinolinesulphonamide] and HA-1004[N-(2-guanidinoethyl)-5-isoquinolinesulphonamide], inhibitors of cAMP-dependent protein kinase (PKA), attenuated the ability
of forskolin to inhibit the 5-HT-stimulated accumulation of IPs. These results suggest that activation of cAMP/PKA was involved
in these inhibitory effects of forskolin. The AlF4
−-induced accumulation of IPs was inhibited by forskolin, suggesting that G protein(s) are directly activated by AlF4
−- and uncoupled from phospholipase C by forskolin treatment. These results suggest that activation of cAMP/PKA might inhibit
the 5-HT-stimulated phosphoinositide breakdown and consequently reduce the [Ca2+]i increase or inhibit both responses independently.
Received: 14 March 1996/Accepted: 10 April 1996 相似文献
33.
INTRODUCTIONAdultRespiratoryDistressSyndrome(ARDS)isanacuteprogressiverespiratoryfailurecausedbymanyreasons.Thetherapeuticactionofthissyndromeisuncertain,becausethemechanismisnotwellknown.Thatis,theprognosisiscritical,themortailityisquiteheigh(50%f)ti--63'Butintherecenttenyears,manyscholarsinourcountryhavehadmuchexperienceintheaspectofusinganisodaminetorescueARDSpatientsandhavedecreasedthemortality(')'Howeveverthescholarsexplaintheprincipleofitindifferentways'Thechangesofmicrovascula… 相似文献
34.
C K Lin J S Lin S Y Chen M L Jiang C F Chiu 《Archives of pathology & laboratory medicine》1992,116(10):1030-1032
In a total group of 415 subjects (100 normal controls, 115 with iron deficiency anemia, 100 with the alpha-thalassemia trait, and 100 with the beta-thalassemia trait), the following indexes were analyzed: hemoglobin distribution width, red blood cell distribution width (RDW)-coefficient of variation, and RDW-SD. The hemoglobin distribution width and RDW-coefficient of variation were examined with a laser light scattering system (Technicon H1), whereas the RDW-SD was determined with an impedance autoanalyzer (Sysmex M-2000). All of these parameters helped, to some extent, in the differential diagnosis of microcytic anemia. However, our data suggested a low RDW-SD might provide significantly more value in differentiating thalassemia traits from iron deficiency anemia, as well as from normal controls, while the hemoglobin distribution width gave no help in the differential diagnosis between iron deficiency anemia and the beta-thalassemia trait. 相似文献
35.
Identification of 6 new mutations in the iduronate sulfatase gene. Mutation in brief no. 233. Online
Vallance HD Bernard L Rashed M Chiu D Le G Toone J Applegarth DA Coulter-Mackie M 《Human mutation》1999,13(4):338
Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. We sequenced genomic DNA and RT-PCR products in the iduronate sulfatase (IDS) gene in 6 unrelated patients with Hunter syndrome to assess genotype/phenotype relationships and offer carrier testing where required. Six novel mutations were identified: four missense mutations, one four-base pair deletion (596-599delAACA) and a cryptic splice site mutation. Three of the missense mutations were significant amino acid substitutions (S143F, S491F, E341K) of which the latter two involve amino acids conserved amongst sulfatase enzymes. The patients identified with these mutations all had a severe clinical phenotype. One missense mutation with a minimal amino acid substitution (H342Y), in a non-conserved region of the gene, was associated with a mild clinical phenotype. We identified a novel cryptic splice site (IVS5+934G>A) with some normal (wild type) mRNA processing. We predict that the normal mRNA product confered some residual functional enzyme, resulting in a mild phenotype associated with the absence of overt central nervous system disease. 相似文献
36.
AIMS: To define epidemiology, clinical disease, and outcome of gemella bacteraemia by 16S rRNA gene sequencing. To examine the usefulness of the Vitek, API, and ATB systems in identifying two gemella species. METHODS: All alpha haemolytic streptococci other than Streptococcus pneumoniae isolated from blood cultures during a six year period were identified by conventional biochemical methods, the Vitek system, and the API system. 16S rRNA gene sequencing was performed on all isolates identified by both kits as gemella with >or= 95% confidence or by either kit as any bacterial species with < 95% confidence. The ATB expression system was used to identify the two isolates that were defined as gemella species by 16S rRNA gene sequencing. RESULTS: Of the 302 alpha haemolytic streptococci other than S pneumoniae isolated, one was identified as Gemella morbillorum, and another as Gemella haemolysans by 16S rRNA gene sequencing. The patient with monomicrobial G morbillorum bacteraemia was a 66 year old man with community acquired infective endocarditis with septic thromboemboli. The patient with G haemolysans bacteraemia was a 41 year old woman with hospital acquired polymicrobial bacteraemia during the neutropenic period of an autologous bone marrow transplant for non-Hodgkin's lymphoma, the first case of its kind in the English literature. The API and ATB expression systems only identified the second strain as G haemolysans at 94% and 99% confidence, respectively, whereas the Vitek system identified none of the two strains correctly at > 70% confidence. CONCLUSIONS: Gemella bacteraemia is uncommon. 16S rRNA gene sequencing is the method of choice for identification of gemella and gemella-like isolates. 相似文献
37.
C W Wu C C Chiu W Y Lui F K P'eng S R Wang 《Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand》1988,6(1):29-32
Lack of lymphocyte infiltration into gastric cancer tissue appears to be an ominous prognostic indicator. The effects of gastric cancer cells on PHA-induced lymphocyte proliferation were studied. Peripheral lymphocytes were co-cultured for 72 hours with either gastric cancer cells or normal mucosal cells. Pairs of cancerous and normal mucosal cells from stomachs of eight patients, were separately co-cultured with peripheral lymphocytes either from patients or from normal volunteers. The degree of PHA-induced lymphocyte proliferation was measured by 3H-thymidine incorporation. The lymphocyte proliferation was inhibited by the presence of either gastric cancerous or normal mucosal cells in a dose-related manner. The lymphocytes from the normals proliferated twice as much as did the lymphocytes from the patients. The isotope incorporation occurred in lymphocytes rather than in gastric cells since the later incorporated insignificant amounts of isotope. There was no difference between gastric cancerous or normal mucosal cells inhibiting the proliferation of either normal or patients' lymphocytes (p greater than 0.05). In conclusion, gastric cancerous cells (up to 10(6)/ml) have no enhanced inhibition on lymphocyte proliferation when compared with normal gastric mucosal cells. 相似文献
38.
Experimental autoimmune encephalomyelitis in mice lacking glial fibrillary acidic protein is characterized by a more severe clinical course and an infiltrative central nervous system lesion. 总被引:3,自引:0,他引:3 下载免费PDF全文
W. Liedtke W. Edelmann F. C. Chiu R. Kucherlapati C. S. Raine 《The American journal of pathology》1998,152(1):251-259
Insights into the role of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), have only recently emerged with reports on subtle abnormalities in GFAP-deficient mice, including the documentation of defective long-term maintenance of central nervous system myelination. Here, we extend these observations by examining the astroglial response in GFAP-/- mice with autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Clinically, the monophasic disease was more severe in GFAP-/- mice than in wild-type littermates despite increased remyelination in the former. More in keeping with the clinical course was the observation of an infiltrative EAE lesion in GFAP-/- mice. GFAP-/- astrocytes had a reduced cytoarchitectural stability as evidenced by less abundant and irregularly spaced hemidesmosomes. The blunt GFAP-/- astrocyte processes possessed intermediate filaments consisting mainly of vimentin, though to a lesser degree than in the wild-type. In contrast, in wild-type littermates, GFAP was most abundant and nestin occurred at lower levels. Taken together, the present study introduces the novel concepts that GFAP plays an important role in the control of clinical disease associated with formation of a clearly defined edge to the EAE lesion and that GFAP is operative in the regulation of the intermediate filament components in reactive fibrillary astrogliosis. 相似文献
39.
Concentrations of endometrial protein PP 14 and CA-125 in uterine flushings performed in natural and stimulated cycles 总被引:3,自引:0,他引:3
BACKGROUND: Impaired implantation in assisted reproduction cycles with high serum estradiol (E(2)) concentrations may be attributed to abnormal endometrial development. This study compared concentrations of endometrial proteins in uterine flushings of infertile patients between natural and stimulated cycles. METHODS: Patients received a standard regimen of ovarian stimulation. Seven days after the LH surge in natural cycles or the hCG injection in stimulated cycles, uterine flushings were performed by slowly injecting and aspirating normal saline through a paediatric Foley catheter. Natural cycles were considered as group A whereas stimulated cycles with serum E(2) <20 000 pmol/l and serum E(2) >20 000 pmol/l were classified as groups B and C respectively. PP 14 and CA-125 in uterine flushings were measured and expressed per total protein content. RESULTS: Concentrations of the total protein, PP 14 and CA-125 in the uterine flushings were similar among the three groups. PP 14 per total protein in the uterine flushings was significantly correlated with serum E(2) on the day of hCG (r = 0.459; P = 0.009) in natural cycles only but not in stimulated cycles. CONCLUSION: There was no significant difference between natural and stimulated cycles in concentrations of PP 14 and CA-125 in uterine flushings performed in the mid-luteal phase. 相似文献
40.
DNA polymerase mu gene expression in B-cell non-Hodgkin's lymphomas: an analysis utilizing in situ hybridization 下载免费PDF全文
Chiu A Pan L Li Z Ely S Chadburn A Knowles DM 《The American journal of pathology》2002,161(4):1349-1355
DNA polymerase mu (pol mu) is a novel error-prone DNA repair enzyme bearing significant structural homology with terminal deoxynucleotidyltransferase. Whereas other human error-prone DNA polymerases identified thus far show no preferential lymphoid tissue distribution, the highest levels of pol mu mRNA have been detected in peripheral lymphoid tissues, particularly germinal center B cells. Conceivably, up-regulation of the pol mu gene may be biologically significant in lymphomagenesis, especially in the development of B-cell non-Hodgkin's lymphomas (B-NHLs), because of enhanced error-prone DNA repair activities. To explore this possibility, we generated a digoxigenin-labeled riboprobe to pol mu mRNA and used the probe and in situ hybridization to examine the expression pattern of the pol mu gene in formalin-fixed, paraffin-embedded tissue sections of 37 B-NHLs. This included eight chronic lymphocytic leukemia/small lymphocytic lymphomas, six mantle cell lymphomas, seven follicular lymphomas, nine diffuse large B-cell lymphomas, three splenic marginal zone lymphomas, two Burkitt's lymphomas, and two precursor B-lymphoblastic lymphomas. We also correlated the pol mu mRNA expression levels with the tumor proliferation index, which was assessed in each case by image analysis of Ki-67 immunostained slides. Nineteen of 21 (90%) B-NHLs arising from postgerminal center B cells (follicular lymphomas, diffuse large B-cell lymphomas, splenic marginal zone lymphomas, and Burkitt's lymphomas) exhibited high expression of pol mu mRNA. In contrast, only 2 of 16 (13%) B-NHLs arising from pregerminal center B cells (chronic lymphocytic leukemia/small lymphocytic lymphomas, mantle cell lymphomas, and precursor B-lymphoblastic lymphomas) expressed significant levels of pol mu mRNA. Pol mu gene expression did not seem to correlate with the proliferation index, especially because a significant level of pol mu mRNA was not detected in either case of precursor B-lymphoblastic lymphomas. In conclusion, pol mu gene expression is highly associated with B-NHLs of postgerminal center B-cell derivation. Furthermore, the expression level is independent of the proliferation rate and thus is unrelated to the biological aggressiveness of the tumors. These findings, along with the error-prone nature of the enzyme, suggest that up-regulation of pol mu gene expression may be a contributing factor to the pathogenesis of a subset of B-NHLs through DNA repair-associated genomic instability. 相似文献