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61.
62.
Kinuko Iwasa Yumi Nishiyama Momoyo Ichimaru Masataka Moriyasu Hye-Sook Kim Yusuke Wataya Takao Yamori Turuo Takashi Dong-Ung Lee 《European journal of medicinal chemistry》1999,34(12):1077
Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, OCOOEt, and OCON(Me)2 reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 > 7 and 8 > 1. 相似文献
63.
Nakazato A Ohta K Sekiguchi Y Okuyama S Chaki S Kawashima Y Hatayama K 《Journal of medicinal chemistry》1999,42(6):1076-1087
sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce structural flexibility for the nitrogen atom and to bridge two benzene rings with a -CH2O- bond to maintain the planar structure. In light of the evidence, N, N-dipropyl-2-(4-methoxy-3-benzyloxylphenyl)ethylamine hydrochloride 10b was designed. Since compound 10b had eliminated a biphenyl bond of 6H-dibenzo[b,d]pyran derivative 2a, it might be more released from the rigid structure of apomorphine 1 than compound 2a. The chemical modification of compound 10b led to the discovery that N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxyl)phenyl]ethylamine hydrochloride 10g (NE- 100), the best compound among arylalkoxyphenylalkylamine derivatives 3, had a high and selective affinity for sigma receptor and had a potent activity in an animal model when the drug was given orally. We report here the design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine derivatives 3. 相似文献
64.
Tsuji Y Satoh H Itoh N Sekiguchi Y Nagasawa K 《Psychiatry and clinical neurosciences》2000,54(3):276-277
In order to detect rapid eye movements (REM) automatically, the Discrete Wavelet Transform was applied to each 8-s segment of electrooculogram (EOG) data for 30 min of 8 h of normal sleep. The Haar function was used as an analysing wavelet because this function is similar to the REM waveform. By shifting the phase of the analysing wavelet by pi/4 of the function, 96% of REM could be detected. The artifacts caused by body movements could be detected simultaneously by this method. Computing time required for the detection of REM was only 11 s for 30 min EOG data. 相似文献
65.
Yusuke Demizu Kazufumi Kagawa Yasuo Ejima Hideki Nishimura Ryohei Sasaki Toshinori Soejima Toshihiro Yanou Masakazu Shimizu Yoshiya Furusawa Yoshio Hishikawa Kazuro Sugimura 《Radiotherapy and oncology》2004,71(2):207-211
We investigated the biological effect of combining carbon-beam and X-ray in vitro. The results showed that when we employed Gray equivalent as the indication of therapeutic dose, the effects could be explained with simple additive way in the treatment plan. This fact provides important information about the combined therapy of carbon-beam and X-ray. 相似文献
66.
Ogata T Kurabayashi M Hoshino YI Sekiguchi KI Kawai-Kowase K Ishikawa S Morishita Y Nagai R 《Transplantation》2000,70(11):1653-1656
67.
Loss of expression of DNA repair enzymes MGMT,hMLH1, and hMSH2 during tumor progression in gastric cancer 总被引:11,自引:0,他引:11
Yoshihiko Kitajima Kohji Miyazaki Shiroh Matsukura Masayuki Tanaka Mutsuo Sekiguchi 《Gastric cancer》2003,6(2):86-95
BACKGROUND: Disorders of the DNA repair system that protects against alkylating mutagens are known to play an important role in carcinogenesis. METHODS: We investigated the expression of the DNA repair enzyme that protects against alkylating mutagens, O(6)-methylguanine DNA methyltransferase (MGMT), and the mismatch repair (MMR) enzymes, hMLH1 and hMSH2, in 135 gastric cancer specimens by immunohistochemical means. RESULTS: The immunoreactivity of MGMT and MMR proteins correlated significantly with several clinicopathologic factors. The survival curve in 116 patients showed that a loss of MGMT or hMLH1, but not of hMSH2, correlated with a poor prognosis. Combined evaluation of MGMT and hMLH1 revealed that the survival of patients with negative status for both MGMT and hMLH1 was shortest. However, this significant association between patient survival and MGMT or hMLH1 expression disappeared when early and advanced cancers were separately analyzed, indicating that synchronous losses of MGMT and hMLH1 increase during tumor progression and stage. Further evaluation according to histologic type revealed that loss of MGMT, hMLH1, and hMSH2 expression significantly differed between early and advanced cancer in differentiated-type cancers. In contrast, in undifferentiated-type cancer, loss of MGMT and MMR expression was frequently found even in intramucosal (m) cancer, and no significant difference was found in loss of hMLH1 and hMSH2 between early and advanced cancer. CONCLUSION: These findings demonstrate that the reduced expression of MGMT, hMLH1, and hMSH2 in differentiated-type cancer may play an important role during tumor progression between the early and advanced stage. On the other hand, in undifferentiated-type cancer, loss of MGMT and the MMR proteins appears to be an important event at carcinogenesis or at an earlier step of tumor progression. 相似文献
68.
Takashi Sekiguchi Makoto Noguchi Kenji Nakamori Gen-iku Kohama 《International journal of clinical oncology / Japan Society of Clinical Oncology》1997,2(1):21-28
Background Changes in interstitial collagen in human oral cancer have not yet been fully studied. We examined the relationship between
the degree of interstitial collagen deposition at the invading edge of the tumor, and the clinical and pathologic findings
in oral squamous cell carcinoma. We also investigated the therapeutic implication of the changes in distribution patterns
of collagen deposition by comparing biopsy specimens and surgical specimens.
Methods Immunohistochemical staining was performed by the streptavidin-biotin method using antibody against human type I collagen
for visualizing interstitial collagen in 50 biopsy and 45 surgical specimens.
Results Carcinomas with scanty interstitial collagen in biopsy specimens tended to have highly malignant characteristics. Large carcinomas
with scanty deposition both in biopsy and surgical specimens were likely to have positive resection margins in spite of radical
surgery.
Conclusion Immunostaining patterns for type I collagen of oral squamous cell carcinomas can provide information of importance in determining
safe resection margins. 相似文献
69.
70.
Daisuke Tamanoi Koichi Saruwatari Kosuke Imamura Ryo Sato Takuya Jodai Shohei Hamada Yusuke Tomita Sho Saeki Shikiko Ueno Yuji Yonemura Hidenori Ichiyasu Takuro Sakagami 《Internal medicine (Tokyo, Japan)》2022,61(11):1731
The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4+ and CD8+ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs. 相似文献