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41.
Tsukamoto F Shiba E Taguchi T Sugimoto T Watanabe T Kim SJ Tanji Y Kimoto Y Izukura M Takai SI 《Breast cancer (Tokyo, Japan)》1997,4(4):259-263
Overexpression of P-glycoprotein (Pgp) in tumors is one of the major mechanisms which mediates the multidrug resistance (MDR)
phenotype. To evaluate the prognostic significance of Pgp in breast cancer, Pgp expression was examined in paraffin-embedded
tissue sections of 94 breast cancer specimens by immunohistochemistry. Tissue specimens were obtained by mastectomy without
preoperative chemotherapy. UIC2 monoclonal antibody which recognizes an extracellular epitope of human Pgp was employed. Of
the 94 breast cancer specimens, 35 (37.2%) were positive for Pgp expression. Pgp expression had no correlation with menopausal
or hormone receptor status, axillary lymph node involvement or tumor size. However, a significant correlation was observed
between Pgp expression and disease relapse (p = 0.0322). Pgp-positive patients showed a significantly shorter disease-free survival period than Pgp-negative patients by
the Kaplan-Meier method (p = 0.0433). These results suggest that immunohistochemical detection of Pgp in breast cancer tissue may have prognostic value
after radical operation. 相似文献
42.
Liver Targeting of Interferon Through Pullulan Conjugation 总被引:1,自引:0,他引:1
Xi Keli Tabata Yasuhiko Uno Kazuko Yoshimoto Miwa Kishida Tsunataro Sokawa Yoshihiro Ikada Yoshito 《Pharmaceutical research》1996,13(12):1846-1850
Purpose. The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver.
Methods. Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2,5-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated.
Results. The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7–9 % of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice.
Conclusions. IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein. 相似文献
43.
I Nakao A Wakui T Hattori K Sugimachi T Saito 《Gan to kagaku ryoho. Cancer & chemotherapy》1991,18(8):1325-1332
A multi-institutional collaborative phase II study of (2"R)-4-O-tetrahydropyranyladriamycin (THP) was performed by intravenous administration to patients with advanced or recurrent gastric cancer. The administration schedules were (1) 40-60 mg/body every 3 or 4 weeks and (2) 20-40 mg/body once a week. Of 58 registered patients, 49 cases were eligible and 37 cases were evaluable for response. The therapeutic results were 1 CR, 4 PR, 14 NC and 18 PD. The response rate of the evaluable cases was 13.5%. The side effects were mainly bone marrow suppression and digestive symptoms. In particular, the frequency of leukopenia was a high 75.5%, while there was a decrease in hemoglobin in 38.8% and anorexia in 30.6%. The frequency and severity of alopecia, which is a known problem with anthracyclines, were slight, and no abnormal electrocardiograms were observed. 相似文献
44.
Damon R Demady Ezra R Lowe Andrew C Everett Scott S Billecke Yasuhiko Kamada Anwar Y Dunbar Yoichi Osawa 《Drug metabolism and disposition》2003,31(7):932-937
It has been shown that administration of cigarette smoke to rats leads to loss of neuronal nitric-oxide synthase (nNOS) activity and nNOS protein in penile tissue. The exact mechanism for this loss of activity and protein is not known. In the current study, we investigated whether extracts prepared from cigarette smoke or from the cigarette itself could directly inhibit nNOS activity. We discovered that the cigarette smoke extract and the cigarette extract cause a time-, concentration-, and calmodulin-dependent inactivation of nNOS in an in vitro system containing the purified enzyme. L-Arginine, but not D-arginine, protects nNOS from this time-dependent inactivation, suggesting an active site directed event. The kinetics of inactivation are consistent with the metabolism-based or suicide inactivation of nNOS. Based on studies with other metabolism-based inactivators, this cigarette-mediated inactivation may render nNOS more susceptible to proteasomal degradation and thereby may explain the loss of nNOS protein in vivo. The component(s) responsible for nNOS inactivation is not volatile, is not retained by a 3,000 molecular weight cut-off membrane, binds to activated charcoal, and is highly water-soluble under both acidic and basic conditions. The discovery of a direct inactivation of nNOS by an organic, cationic compound(s) present in tobacco and tobacco smoke provides a basis for further study of not only the mechanisms responsible for the biological effects of tobacco but also a search for a potentially novel inactivator of nNOS. 相似文献
45.
Expression level of valosin-containing protein is strongly associated with progression and prognosis of gastric carcinoma. 总被引:9,自引:0,他引:9
Shinji Yamamoto Yasuhiko Tomita Yoshihiko Hoshida Shuji Takiguchi Yoshiyuki Fujiwara Takushi Yasuda Masahiko Yano Shoji Nakamori Masato Sakon Morito Monden Katsuyuki Aozasa 《Journal of clinical oncology》2003,21(13):2537-2544
PURPOSE: Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined. PATIENTS AND METHODS: VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. RESULTS: Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P <.0001), undifferentiated histologic subtype (P <.05), presence of vascular and lymphatic invasion (P <.0001 for both), presence of lymph node metastasis (P <.0001), deep tumor invasion (P <.0001), and poorer disease-free and overall survivals (P <.0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1; P <.01 and P <.05, respectively) and advanced (pT2-4; P <.05 for both) group of pathologic tumor-node-metastasis system classification. CONCLUSION: The prognostic significance of VCP expression level in GC was demonstrated. 相似文献
46.
Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence. 总被引:11,自引:0,他引:11
47.
Yasuhiko Kano Miyuki Akutsu Saburo Tsunoda Koyoshi Mori Kenichi Suzuki Ken-Ichi Adachi 《Cancer chemotherapy and pharmacology》1998,42(2):91-98
Paclitaxel and irinotecan are important new anticancer agents. The combination of these two agents has been considered for
use against a variety of advanced solid tumors. Since the schedule-dependent effects of this combination may be crucial to
its use, we studied the interaction of paclitaxel and SN-38 (the active metabolite of irinotecan) in various schedules in
four human cancer cell lines in culture. Cell growth inhibition after 5 days was determined using an MTT assay. The effects
of drug combinations at the IC80 level were analyzed by the isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h produced antagonistic
(subadditive and protective) effects in the human lung cancer cell line A549, the breast cancer cell line MCF7, and the colon
cancer cell line WiDr, and produced additive effects in the ovarian cancer cell line PA1. Sequential exposure to paclitaxel
for 24 h followed by SN-38 for 24 h, and the reverse sequence, produced additive effects in all four cell lines. These findings
suggest that sequential administration, not simultaneous administration, may be the appropriate schedule for the therapeutic
combination of paclitaxel and irinotecan. Continued preclinical and clinical studies should provide further insights and assist
in determining the optimal schedule for this combination in clinical use.
Received: 25 February 1997 / Accepted: 6 November 1997 相似文献
48.
Nafamostat mesilate suppresses NF-kappaB activation and NO overproduction in LPS-treated macrophages 总被引:2,自引:0,他引:2
Noguchi S Nakatsuka M Konishi H Kamada Y Chekir C Kudo T 《International immunopharmacology》2003,3(9):1335-1344
Nafamostat mesilate (NM), a clinically used serine protease inhibitor, suppressed the overproduction of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in RAW264.7 murine macrophages treated with lipopolysaccharide (LPS, 100 ng/ml); however, it had little effect on endothelial NOS (eNOS) in human umbilical vein endothelial cells (HUVEC). Electrophoretic mobility shift assay (EMSA) revealed that LPS activated nuclear factor-kappaB (NF-kappaB) in RAW264.7 cells and that this activation was suppressed by nafamostat mesilate. Western blotting showed that nafamostat mesilate suppressed the phosphorylation and degradation of inhibitor kappaB-alpha (IkappaB-alpha), which holds NF-kappaB in the cytoplasm in an inactivated state. Our observations suggest that nafamostat mesilate is a candidate agent for various diseases such as ischemia-reperfusion, graft rejection, inflammatory diseases, and autoimmune diseases, in which iNOS and/or NF-kappaB are upregulated. 相似文献
49.
Naoyuki Kanayama Fumiaki Isohashi Yasuo Yoshioka Sungjae Baek Masashi Chatani Tadayuki Kotsuma Eiichi Tanaka Ken Yoshida Yuji Seo Osamu Suzuki Seiji Mabuchi Yasuhiko Shiki Keiji Tatsumi Tadashi Kimura Teruki Teshima Kazuhiko Ogawa 《Journal of radiation research》2015,56(2):346-353
The purpose of this study was to determine the outcomes and optimal practice patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and 2012, 49 patients were treated with definitive radiotherapy for primary vaginal cancer in three hospitals. Of these, 15 patients (31%) had clinically positive regional lymph node metastasis. A total of 34 patients (70%) received external beam radiotherapy with high-dose-rate brachytherapy (interstitial or intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated with local radiotherapy. The median follow-up was 33 months (range: 1–169 months). The 3-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate analysis, the histological type (P = 0.044) was significant risk factors for LRC. In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients (38%) who did not undergo prophylactic lymph node irradiation had lymph node recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic pelvic irradiation. For Stage III–IV tumors, the local recurrence rate was 50% and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or clinical Stage N1 had a higher recurrence rate with treatment using a single modality compared with the recurrence rate using combined modalities. In conclusion, our treatment outcomes for vaginal cancer were acceptable, but external beam radiotherapy with brachytherapy (interstitial or intracavitary) was needed regardless of FIGO stage. Improvement of treatment outcomes in cases of FIGO Stage III or IV remains a significant challenge. 相似文献
50.
Chikara Kunisaki Hirochika Makino Ryo Takagawa Kei Sato Mayumi Kawamata Amane Kanazawa Naoto Yamamoto Yasuhiko Nagano Shoichi Fujii Hidetaka A. Ono Hirotoshi Akiyama Hiroshi Shimada 《Surgical endoscopy》2009,23(9):2085-2093
Background Some studies have found high incidences of intraoperative and postoperative complications for patients with gastric cancer.
To determine the predictive factors for the surgical complications of laparoscopic gastric surgery, surgical outcomes were
evaluated.
Methods Between April 2002 and December 2007, 152 patients with preoperatively diagnosed early gastric cancer who underwent laparoscopy-assisted
distal gastrectomy (LADG) were enrolled. Visceral (VFA) and subcutaneous fat areas (SFA) were assessed by Fat Scan software.
The predictive factors for surgical complications of LADG were evaluated by univariate and logistic regression analyses.
Results Of 152 patients, conversion to open surgery due to uncontrollable bleeding was observed in nine male patients, and postoperative
complications were detected in seven male and one female patient (four anastomotic leakage, two intraabdominal abscess, one
pancreatic fistula, and one lymphorrhea). High body mass index (BMI) and high VFA independently predicted conversion to open
surgery and postoperative complications. VFA was significantly higher, operation time was longer, blood loss was greater,
and SFA was lower in male than in female patients, whereas no significant difference was observed in BMI between male and
female patients.
Conclusions High BMI and high VFA can predict technical difficulties during laparoscopic gastric surgery and postoperative complications.
Particularly, LADG should be performed cautiously to prevent surgical complications for male patients with high VFA. Predictive
impact of VFA should be further determined in a larger set of patients. 相似文献