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61.
H Hirai H Taga Y Endo S Iino M Sugiura S Futagawa 《Gan to kagaku ryoho. Cancer & chemotherapy》1988,15(1):101-108
We studied the effect of UFT (a mixture of Tegafur and uracil at a ratio of 1:4) on hepatocarcinogenesis and alpha-fetoprotein (AFP) production induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in rats. By feeding rats with 3'-MeDAB diet, serum AFP started to appear from week 2-3 and increased until week 5-7, then declined until week 10-11. This phenomenon of a transient appearance of serum AFP is called "primary reaction". After week 11 hepatoma started to develop accompanied with an enormous elevation of serum AFP level until animals die, generally before week 25. Male Donryu strain rats fed a diet containing 0.06% 3'-MeDAB for 10 weeks, and then fed the normal diet. UFT was given by a stomach tube once a day for five days a week. Blood was collected from the tail vein every other week and serum AFP was measured by Rocket electrophoresis technique. When the administration of UFT (10 mg or 20 mg/kg/day) was started simultaneously with feeding 3'-MeDAB diet, the primary reaction was somewhat suppressed, and after week 11 development of hepatoma and elevation of AFP were markedly inhibited. The administration of UFT of a high dose (40 mg/kg/day) caused the death of animals in 7 weeks probably because of its toxicity. When the administration of UFT (10 mg or 20 mg/kg/day) was started after finish of feeding 3'-MeDAB diet for 10 weeks, the drug was not effective. These results show that if the administration of UFT was commenced at the same time with feeding 3'-MeDAB diet, the hepatocarcinogenesis and AFP production are strongly inhibited. 相似文献
62.
Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated byβ protein immunostain 总被引:5,自引:0,他引:5
Summary We studied senile plaques (SP) in the cerebella of six autopsied subjects with Alzheimer-type dementia (ATD) and ten non-ATD autopsied subjects between the ages of 78 and 90. Neither SP nor amyloid angiopathy (AA) was observed in any of the non-ATD subjects. In the four of the six ATD subjects, diffuse plaques in the molecular layer were seen as ill-defined areas of fine fibrillar materials by protein immunostaining with formic acid pretreatment, the modified Bielschowsky stain, and periodic acid-methenamine silver (PAM) stain. The plaques were not visible with Bodian, Congo red, or periodic acid-Schiff stains. Compact plaques in the Purkinje cell or in the granular cell layers were found in three of the six subjects. Their amyloid core was often surrounded by areolar amyloid deposits. AA was observed in three of the six subjects. The argyrophilia of the diffuse and compact plaques, demonstrated by the modified Bielschowsky and PAM stains, became undetectable when the sections were first treated with formic acid. Such treatment made the plaques immunoreactive with protein antiserum. The findings suggested that cerebellar diffuse plaques and compact plaques consist mainly of an amyloid component, and are characteristic of ATD. 相似文献
63.
Yoshihiro Katagiri Kazuhide Mabuchi Tadanori Itakura Kohji Naora Kikuo Iwamoto Yoshimasa Nozu Shun-ichi Hirai Nobumasa Ikeda Toshio Kawai 《Cancer chemotherapy and pharmacology》1989,24(4):238-242
Summary Physicochemical properties of two types of adriamycin preparation, suspensions and emulsions prepared for i.a. chemotherapy of hepatocellular cacinoma, were investigated. A suspension was prepared by dispersing adriamycin directly into the lipid contrast medium, Lipiodol, whereas an emulsion was obtained by emulsifying an aqueous solution of adriamycin into Lipiodol. The dispersibility of the drug in each preparation was examined microscopically. The chemical stability of and drug release from the preparation were determined by high-performance liquid chromatography and spectrophotometry, respectively. The suspension was then given to ten patients with primary hepatocellular carcinoma. The suspension maintained good dispersibility without coagulation of drug particles, whereas coalescence of aqueous droplets and the resultant phase separation occurred 4 h after preparation of the emulsion. Both preparations maintained the initial drug content for at least 1 week at room temperature. The release of adriamycin was more prolonged in the suspension than in the emulsion. After i.a. administration of the suspension, a selective accumulation of Lipiodol in the tumor and decrease in serum -fetoprotein (AFP) levels were found in most patients. A significant amount of adriamycin was still detected in hepatic speciments resected from two patients 1 and 2 months after treatment. These findings suggest that the adriamycin-Lipiodol suspension may be a useful preparation for targeting chemotherapy to hepatocellular carcinoma. 相似文献
64.
Uchida Y Ohshima T Sasaki Y Suzuki H Yanai S Yamashita N Nakamura F Takei K Ihara Y Mikoshiba K Kolattukudy P Honnorat J Goshima Y 《Genes to cells : devoted to molecular & cellular mechanisms》2005,10(2):165-179
Collapsin response mediating protein-2 (CRMP2) has been identified as an intracellular protein mediating Semaphorin3A (Sema3A), a repulsive guidance molecule. In this study, we demonstrate that cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta (GSK3beta) plays a critical role in Sema3A signalling. In In vitro kinase assay, Cdk5 phosphorylated CRMP2 at Ser522, while GSK3beta did not induce any phosphorylation of CRMP2. Phosphorylation by GSK3beta was exclusively observed in Cdk5-phosphorylated CRMP2, but barely in CRMP2T509A. These results indicate that Cdk5 primarily phosphorylates CRMP2 at Ser522 and GSK3beta secondarily phosphorylates at Thr509. The dual-phosphorylated CRMP2, but not non-phosphorylated or single-phosphorylated CRMP2, is recognized with the antibody 3F4, which is highly reactive with the neurofibrillary tangles of Alzheimer's disease. 3F4 recognized the CRMP2 in the wild-type but not cdk5-/- mouse embryonic brain lysates. The phosphorylation of CRMP2 at Ser522 caused reduction of its affinity to tubulin. In dorsal root ganglion neurones, Sema3A stimulation enhanced the levels of the phosphorylated form of CRMP2 detected by 3F4. Over-expression of CRMP2 mutant substituting either Ser522 or Thr509 to Ala attenuates Sema3A-induced growth cone collapse response. These results suggest that the sequential phosphorylation of CRMP is an important process of Sema3A signalling and the same mechanism may have some relevance to the pathological aggregation of the microtubule-associated proteins. 相似文献
65.
Boxall S Stanton T Hirai K Ward V Yasui T Tahara H Tamori A Nishiguchi S Shiomi S Ishiko O Inaba M Nishizawa Y Dawes R Bodmer W Beverley PC Tchilian EZ 《Human molecular genetics》2004,13(20):2377-2384
The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance. 相似文献
66.
Hery?Wijayanto Yuriko?Hirai Yosirou?Kamanaka Akira?Katho Dondin?Sajuthi Hirohisa?HiraiEmail author 《Chromosome research》2005,13(7):715-722
The course of chromosome evolution in small apes is still not clear, though painting analyses have opened the way for elucidating
the puzzle. Even the C-banding pattern of the lar-group of gibbons (the genus Hylobates) is not clarified yet, although our previous studies suggested that lar-group gibbons have a unique C-banding pattern. We
therefore made observations to establish C-banded karyotypes of the agile gibbons included in the lar-group. The data were
compared with those of siamangs (the genus Symphalangus), which carry distinctive C-bands, to determine the chromosomal patterns in each group. C-banded chromosomes of agile gibbons
showed several terminal, interstitial and paracentric bands, whose patterns are specific for each chromosome, whereas the
C-bands of siamangs were located only at the terminal and centromeric regions in most chromosomes. Moreover, the C-bands of
agile gibbons and siamangs were shown to be G+C-rich and A+T-rich DNA, respectively, by DAPI/C-band sequential staining. Additionally,
PRINS labelling with a telomere primer revealed that agile gibbons have telomeric DNA only at chromosome ends where there
is no C-band (non-telomeric heterochromatin), whereas the telomeric DNA of siamangs is located in the terminal C-banded regions
(telomeric heterochromatin). Although the evolutionary mechanisms in small apes are still unknown, C-banding patterns and
distribution of telomeric DNA sequences should provide valuable data to deduce the evolutionary pathways of small apes. 相似文献
67.
68.
BACKGROUND: Bronchial asthma is characterized by airway inflammation, notably because of eosinophils and T cells. Thymus and activation-regulated chemokine (TARC) is known to selectively attract Th2 cells, and is increased in response to interleukin (IL)-4 and IL-13, which share a common receptor, IL-4 receptor alpha (IL-4Ralpha). While corticosteroids have proven, very effective in modifying airway inflammation, the effect of corticosteroids on TARC in asthmatics has been little studied. OBJECTIVE: We examined the effects of inhaled budesonide (BUD) on the expression of TARC and the number of inflammatory cells in bronchial biopsy specimens taken from asthma patients. METHODS: Inhaled BUD 800 mug daily, or placebo was administered for 3 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined by immunocytochemistry. RESULTS: We observed a significant decrease in the epithelial expression of TARC (P < 0.01) in the BUD group compared with the placebo group. This was accompanied by decreases in the number of eosinophils (P < 0.01), CD3(+) T cells (P < 0.05), and CD4(+) T cells (P < 0.01). A significant correlation was found between changes in epithelial TARC and in IL-4Ralpha immunoreactivity (r(s) = 0.66, P < 0.01). CONCLUSIONS: These findings suggest that corticosteroid asthma treatment can reduce infiltration of the airway by inflammatory cells, an effect modulated by down-regulation of bronchial epithelial TARC expression. 相似文献
69.
Kaburaki J Kuwana M Ikeda Y 《Rinsho byori. The Japanese journal of clinical pathology》2003,51(7):639-643
The concept of antiphospholipid syndrome(APS) has been widely accepted. Antiphospholipid antibodies originally included anticardiolipin antibodies and lupus anticoagulants as serological marker of APS. However, recent advances have shown that most pathogenic antiphospholipid antibodies are directed to phospholipid binding proteins such as beta 2-glycoprotein I and prothrombin as well as phospholipids. The preliminary classification criteria for definite APS have been advocated as the "Sapporo criteria". Further prospective investigations are required to re-evaluate the clinical significance of so-called antiphospholipid antibodies. 相似文献
70.
Rapid and efficient generation of lentivirally gene-modified dendritic cells from DC progenitors with bone marrow stromal cells 总被引:4,自引:0,他引:4
Sumimoto H Tsuji T Miyoshi H Hagihara M Takada-Yamazaki R Okamoto S Ikeda Y Takahashi T Kawakami Y 《Journal of immunological methods》2002,271(1-2):153-165
Since dendritic cells (DC) play pivotal roles in both innate and adaptive immunity, DC can be a good target for immuno-gene therapy. However, the optimal generation method for gene-modified DC has not yet been well exploited. CD34+ cells from cord blood (CB), bone marrow (BM), or peripheral blood (PB) were expanded in a medium containing stem cell factor (SCF), flt 3 ligand (Flt3L) and thrombopoietin (TPO) with or without HESS-5, a murine BM stromal cell line, for 2 weeks (the first expansion step), then differentiated to DC in a medium containing granulocyte-macrophage colony-stimulating factor (GM-CSF), flt 3 ligand (Flt3L), stem cell factor (SCF), tumor necrosis factor-alpha (TNF-alpha), IL-4, and lipopolysaccharide (LPS) for 9 days (the second differentiation step). DC progenitors were transduced with human immunodeficiency virus (HIV) vectors at different time points during the second step. Use of HESS-5 during the first step resulted in more DC generation than without it (cell expansion: CB, 10,461 vs. 354-fold; BM, 962 vs. 225-fold; peripheral blood mononuclear cell (PBMC), 8,506 vs. 240-fold; %DC: CB, 83.4% vs. 76.9%; BM, 83.6 vs. 69.8%; PBMC, 85.9 vs. 60.5%). Gene transduction to the in vitro expanded DC progenitors at day 3 during the second step, resulted in better final yield of the gene-modified DC than that to those at day 0 or day 6 (as much as 44% of DC expressed green fluorescence protein (GFP) as a transgene) and the transduction efficiency correlated with endocytic ability and percent of S phase. DC transduced with an HIV vector encoding a melanoma antigen, MART-1, were adequately recognized by specific anti-MART-1 CTL. The two-step culture method with HESS-5 is useful for rapid expansion of DC progenitors and subsequent lentiviral gene transduction to DC. 相似文献