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81.
Akitaka Yamasaki Kumiko Maruyama-Takahashi Kento Nishida Shogo Okazaki Kouki Okita Yasutoshi Akiyama Hideaki Suzuki Yuichi Endo Kazue Masuko Takashi Masuko Yoshihisa Tomioka 《Genes to cells : devoted to molecular & cellular mechanisms》2023,28(5):374-382
Human epidermal growth factor receptor (HER) family proteins are currently major targets of therapeutic monoclonal antibodies against various epithelial cancers. However, the resistance of cancer cells to HER family-targeted therapies, which may be caused by cancer heterogeneity and persistent HER phosphorylation, often reduces overall therapeutic effects. We herein showed that a newly discovered molecular complex between CD98 and HER2 affected HER function and cancer cell growth. The immunoprecipitation of the HER2 or HER3 protein from lysates of SKBR3 breast cancer (BrCa) cells revealed the HER2-CD98 or HER3-CD98 complex. The knockdown of CD98 by small interfering RNAs inhibited the phosphorylation of HER2 in SKBR3 cells. A bispecific antibody (BsAb) that recognized the HER2 and CD98 proteins was constructed from a humanized anti-HER2 (SER4) IgG and an anti-CD98 (HBJ127) single chain variable fragment, and this BsAb significantly inhibited the cell growth of SKBR3 cells. Prior to the inhibition of AKT phosphorylation, BsAb inhibited the phosphorylation of HER2, however, significant inhibition of HER2 phosphorylation was not observed in anti-HER2 pertuzumab, trastuzumab, SER4 or anti-CD98 HBJ127 in SKBR3 cells. The dual targeting of HER2 and CD98 has potential as a new therapeutic strategy for BrCa. 相似文献
82.
Masatsugu Nakamura Keiko Ofuji Tai-ichiro Chikama Teruo Nishida 《British journal of pharmacology》1997,120(4):547-552
- We have previously shown that substance P (SP) and insulin-like growth factor-1 (IGF-1) act synergistically to enhance the migration of rabbit corneal epithelial cells in an organ culture model. The present study was designed to identify the epithelial cell SP receptor that participates in this synergistic effect.
- Rabbit corneal blocks were incubated for 24 h, then the length of the path of epithelial migration was measured. Reagents tried in the TC-199 culture medium, in the presence or absence of IGF-1, were: SP, agonists of tachykinin receptors NK1, NK2 or NK3 and antagonists of tachykinin receptors NK1 or NK2.
- The binding characteristics of SP receptors were examined in rabbit cultured corneal epithelial cells by binding assays with [125I]-SP in the presence or absence of excess unlabelled SP or ligands of NK1, NK2 or NK3 receptors.
- As was demonstrated previously, SP and IGF-1 stimulated epithelial migration when they were added to the culture medium together, but individually they had no effect. NK1 agonists had the same synergistic effect with IGF-1 as did SP, but the NK2 and NK3 agonists did not. Furthermore, the NK1 antagonist abolished the synergistic effect of SP and IGF-1, but the NK2 antagonist had no effect.
- SP bound specifically to rabbit cultured corneal epithelial cells. The binding affinity was 0.44 nM and there were 2.43×104 binding sites per cell. The NK1 ligand competed, in a dose-dependent fashion, with the binding of SP to corneal epithelial cells, but neither the NK2 nor NK3 ligand affected binding.
- We conclude that the SP receptor in rabbit corneal epithelial cells is NK1 and that this receptor participates in the synergistic enhancement of corneal epithelial migration by SP and IGF-1. The precise mechanism(s) of this interaction requires more study. These findings imply that both neural and humoral factors are essential for the maintenance and healing of corneal epithelium.
83.
Shimizu Y Nagata H Umezawa S Nishida M Kikuchi Y Hasumi K Yokokura T 《Oncology reports》1997,4(5):945-948
The aim of the present study was to evaluate cytotoxic agents active for clear cell carcinoma of the ovary (OCCA) which is intrinsically platinum-resistant. We first conducted in vitro chemosensitivity tests assessing antitumor activities of Various agents against OCCA using two cell lines (HAC-2 and KK) established from ascites of patients with pure OCCA. The most potent single agent was SN-38 (active substance of CPT-11 in vivo) in both cell lines. The second most potent agent was mitomycin-C (MMC) followed by doxorubicin (DOX) in HAC-2 and DOX followed by MMC in KK, respectively. In vivo chemosensitivity test of agents on HAC-2 transplanted into BALB/C nude mice demonstrated that MMC was most potent, followed by DOX and CPT-11. Moreover, a combination of CPT-11 and MMC exhibited the highest anti-tumor activity in this animal model. Cisplatin, etoposide, and paclitaxel were found to be ineffective in either the in vitro or in vivo experimental system. Clinical trial with a combination of MMC and CPT-11 are warranted in patients with OCCA. 相似文献
84.
We investigated the interactions in the KOC-2s human ovarian cancer cells on the effect of glucocorticoids, and sex steroid hormones in ovarian carcinomas. At 10(-8) M to 10(-5) M, dexamethasone (Dex) decreased the number of cells by 75-80% (p<0.001). At 10(-8) M and 10(-7) M, hydrocortisone (HC) decreased the number by 50% (p<0.01); at 10(-6) M and 10(-5) M, the decrease in number of cells was 65%. The E-2 decrease in number was not statistically significant. Progesterone (PG) showed at 10(-8) to 10(-6) M an increase in number of cells, however, at 10(-5) M it was decreased by 70% with a significant difference (p<0.001). Dex (10(-8)-10(-5) M), HC (10(-8)-10(-5) M) and PG (10(-5) M) produced internucleosomal cleavage of DNA into fragments with multiples of 180 to 200 bp. The TNF-alpha with addition of Dex (10(-8)-10(-5) M) and HC (10(-8)-10(-5) M) was increased after 24 h, 48 h (p<0.001); however, gradually decrease after 72 h. When PG (10(-8)-10(-5) M) was added, PG (10(-5) M) increased the secretion of TNF-alpha after 72 h. Our findings demonstrate that glucocorticoids, and PG directly induce apoptotic DNA fragmentation of KOC-2s cells. However, the secretion of TNF-alpha and expression of Fas antigen were totally different in these substances. These data provide a basis for future studies on the mechanisms of apoptotic effect of glucocorticoids, and PG and the therapeutic effects of these substances. 相似文献
85.
Oyama T Kawamoto T Mizoue T Nishida K Osaki T Sugio K Yasumoto K Mitsudomi T 《International journal of oncology》1997,11(2):305-309
Cytochrome p4501A1 gene (CYP1A1) and glutathione S-transferase mu gene (GSTM1) are involved in the metabolic activation or detoxification of environmental carcinogens including benzo[a]pyrene in tobacco smoke. Individuals with both Val/Val and C type of CYP1A1 (CYP1A1; Val/Val and CYP1A1; C) or homozygous null (-/-) genotype of GSTM1 gene (GSTM1; -/-) show increased susceptibility to lung cancer. The incidence of p53 gene mutations are related to the smoking index of the lung cancer patients. Therefore we determined genotypes of these enzymes and screened p53 gene mutations in 123 non-small cell lung cancer (NSCLC) patients. p53 gene mutations were found in 35% (43/123) of the patients. The incidence of p53 gene mutation CYP1A1; Val/Val (60.0%), CYP1A1; C (50.0%) tended to be higher than those of CYPIAI; Ile/Ile and Ile/Val (40.4%) or CYP1A1; A and B (40.5%). We conclude that the incidence of the p53 mutations does not seem to be significantly affected by only CYP1A1 or GSTM1 polymorphisms in lung cancer patients. 相似文献
86.
Hiraide H Okamura S Hayashi T Nishida M Tamaki K Tamakuma S 《Breast cancer (Tokyo, Japan)》1994,1(2):103-108
The collagen cross-links, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) excreted in urine have recently been suggested as new markers of bone metastasis. In a pilot study we measured Pyr and D-Pyr in 61 patients with breast cancer, 16 with known bone metastasis and 45 with no recognized metastasis in bone. Twenty healthy female subjects were also measured as controls. The mean values (+/-SD) of Pyr and D-Pyr in the group with bone metastasis were significantly higher (Pyr: p<0.01, D-Pyr: p <0.05) than those in the group without bone metastasis and in the control group. The mean (+/-SD) values of postmenopausal women were significantly higher than those of premenopausal in the group without bone metastasis (p<0.05) and in the control group (p<0.01). Therefore, the effect of menopause should be taken into account in the diagnosis of bone metastasis by assays of Pyr and D-Pyr. Setting the cut-off values (mean + 2SD of the values of control) for pre and postmenopausal patients, the accuracy for Pyr was 71.4% in premenopausal and 75.8% in postmenopausal patients; and for D-Pyr it was 71.4% and 78.8% respectively. We consider that measurement of urinary collagen cross-links assays can contribute to the early detection of metastatic spread to bone in breast cancer. 相似文献
87.
Nishida T Sugiyama T Kataoka A Ushijima K Ueyama T Yakushiji M 《Oncology reports》1995,2(6):1045-1048
The incidence and transplantability of ovarian teratoma in LT/Sv mice were examined following cisplatin treatment at the age of 16 days, and compared to those in the control group. Cisplatin had not affected the emergence of egg cleavage, which simultaneously appeared in the mouse ovaries in both groups. Although 7 teratomas, occasionally transplantable, developed in the control mice aged over 30 days, only 2 tumors occurred in cisplatin-treated mice at the age of 120 days and they were not transplantable. The results suggest that cisplatin might influence the tumorigenic process after egg cleavage, or transplantability of teratoma. 相似文献
88.
A signal separation method for extracting background electroencephalogram (EEG) from EEG containing spikes was proposed. Morphological filters were designed for extracting spike waveforms, and then the background EEG was obtained by subtracting the detected spike waveforms from the EEG with spike. The proposed method was evaluated by using simulated EEG data, which consisted of a summation of EEG without spike and model waveform of typical spike. The background EEG separated by the method was processed by the automatic background EEG interpretation. 相似文献
89.
BACKGROUND: Bacterial cholangitis is frequently associated with serious complications. METHODS: The plasma disappearance rates and the biliary output of bile acids and bilirubin after percutaneous transhepatic biliary drainage (PTBD) were examined in 29 patients with extrahepatic biliary obstruction. RESULTS: Twenty-nine patients were divided into the bacteria-minus (n = 17) and bacteria-plus (n = 12) groups. Decreases in the plasma bile acid and bilirubin levels of the bacteria-minus group (t1/2 = 0.38 and 3.8 days for bile acids and bilirubin, respectively) were faster than those of the bacteria-plus group (t1/2 = 1.7 and 7.5 days). The bile flow rate was significantly increased in the bacteria-plus group compared with the bacteria-minus group. The calculated values of bilirubin and bile acid in the bile were higher in the bacteria-minus group than in the bacteria-plus group. CONCLUSIONS: Bacterial colonization in the bile stimulates bile duct cells to increase bile volume and inhibits the hepatocyte transport activity of bile acids and bilirubin. 相似文献
90.