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Kiyotaka Okuno Norihiko Hirai Yung Sun Lee Dino Tarabar Hideo Ueno Masayuki Yasutomi 《Cancer chemotherapy and pharmacology》1998,42(4):341-344
Purpose: The aim of this study was to identify the route of administration of 5-FU with the greatest pharmacological advantage in
a rat model using noninvasive in vivo 19F nuclear magnetic resonance (NMR) spectroscopy. Methods: 5-FU (50 mg/kg) was administered to anesthetized Wistar rats cannulated into the hepatic artery, portal vein or tail vein
and 11 NMR spectra were acquired from the liver region to 60.5 min every 5.5 min. Results: With systemic i.v. (tail vein) infusion, the 19F-NMR signal for 5-FU from the liver region peaked in the first spectrum (0–5.5 min), and then gradually decreased. The signal
for the 5-FU catabolite α-fluoro-β-alanine (FBAL) gradually increased to the sixth spectrum (0–33.0 min) and then plateaued.
Following portal vein infusion the intensity of the first 5-FU spectrum was twice as high as that following i.v. infusion,
but the intensity decreased and the FBAL signal increased gradually in the sixth spectrum as systemic i.v. infusion. In contrast,
the intensity of the 5-FU signal following hepatic artery infusion was the same as that following portal vein infusion in
the first spectrum, and maintained a strong intensity to the final spectrum (60.5 min). The FBAL signal was detected from
the second spectrum following hepatic artery infusion, but its intensity was significantly weaker than that following i.v.
or portal vein infusion. Conclusions: Hepatic arterial infusion resulted in the active form of 5-FU being present for a longer time and its degradation in the
liver being suppressed compared with the results following portal vein infusion. This catabolic advantage of hepatic areterial
infusion could lead to a more potent anti-tumor activity against liver metastases, but could also lead to significant host
toxicity including biliary toxicity. We recommend that the dose/schedule of 5-FU administered via the hepatic artery should
be adjusted carefully.
Received: 4 August 1997 / Accepted: 16 January 1998 相似文献
84.
Nobuyuki Enomoto Yoshiyuki Takei Kazuyoshi Kon Shunhei Yamashina Satoko Suzuki Kenichi Ikejima Nobuhiro Sato 《Nihon Arukōru Yakubutsu Igakkai zasshi》2005,40(3):213-218
The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially characterized. It now appears that Kupffer cell derived TNF-alpha participates in several aspects of alcoholic liver injury. On the other hand, protease inhibitors have been used successfully for treatment of intractable diseases in which TNF-alpha is involved in the pathogenesis, including ulcerative colitis and Crohn's disease. Here, we will review new evidence for the proposal that serine protease inhibitors prevents alcoholic liver injury via mechanisms dependent on Kupffer cell derived TNF-alpha. 相似文献
85.
R. Kato Y. Okuno C. Kaga M. Kunimatsu T. Kobayashi H. Honda 《Chemical biology & drug design》2005,66(Z1):146-153
Abstract: Despite their low molecular weight and simple structure, peptides regulate vital reactions of various cells. With higher standards of safety and purity required in clinical researches, chemically synthesized peptides are considered as an ideal alternative material for animal‐derived materials in the regulation of cellular events. However, effective high‐throughput assay for studying peptide‐cell interactions has not been established to design peptide with objective function. Here, we report the effectiveness of the utilization of peptide array combined with cell assay for the design of cell‐interactive peptides. As a model case, peptide that regulates tumor cell viability with support‐bound form was explored. By culturing cells on peptide array, we found a novel 5‐mer sequence CNNLP (Cys‐Asp‐Asp‐Leu‐Pro) that strongly inhibits viability of tumor cells (leukemia and adenocarcinoma) from human Fas antigen ligand. We here indicate the advantageous features of peptide array, which are ‘feasibility in examining combinatorial amino acid substitutions’ and ‘indicative data consist of effective and ineffective substitutions from an assay’, contributes greatly for studying peptide‐cell interaction. These features differentiate peptide array from other peptide library screening strategy. As a result, we succeeded in obtaining 29 novel tumor‐growth inhibitory peptides with it solid‐bound form, and structural rules that suggest ideal peptide design for acquiring objective peptide function. 相似文献
86.
Gender difference in alcoholic liver injury] 总被引:1,自引:0,他引:1
Nobuyuki Enomoto Yoshiyuki Takei Shunhei Yamashina Kenichi Ikejima Satoko Suzuki Tsuneo Kitamura Nobuhiro Sato 《Nihon Arukōru Yakubutsu Igakkai zasshi》2004,39(3):163-167
Gender differences of alcoholic liver injury have been described previously, but mechanisms have only partially characterized. For example, it is known that females develop alcoholic liver injury more rapidly and to a greater extent than males. It now appears that estrogen participates in several aspects of this phenomenon. On the other hand, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cell and alcohol-induced liver injury. 相似文献
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Makoto Sugaya Kaoru Funamizu Michihiro Kono Yusuke Okuno Taisuke Kondo Ryusuke Ono Masashi Akiyama Chikako Nishigori Shinichi Sato 《The Journal of dermatology》2021,48(1):96-100
A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions. 相似文献
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