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151.
Ojima I Geng X Wu X Qu C Borella CP Xie H Wilhelm SD Leece BA Bartle LM Goldmacher VS Chari RV 《Journal of medicinal chemistry》2002,45(26):5620-5623
Taxoids bearing methyldisulfanyl(alkanoyl) groups for taxoid-antibody immunoconjugates were designed, synthesized and their activities evaluated. A highly cytotoxic C-10 methyldisulfanylpropanoyl taxoid was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) expressed in human squamous cancers. These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in severe combined immune deficiency mice, resulting in complete inhibition of tumor growth in all the treated mice. 相似文献
152.
Niimi S Hyuga M Kazama H Inagawa M Seki T Ariga T Kobayashi T Hayakawa T 《Biological & pharmaceutical bulletin》2002,25(11):1405-1408
The effect of activins A, AB, and B on hepatocyte growth factor (HGF) synthesis stimulated by 12-O-tetradecanoylphorbol beta-acetate (TPA) was studied in MRC-5 human lung fibroblasts. Activins A, AB, and B inhibited the increase in HGF secretion induced by TPA in different dose-dependent manners and potencies. At 5 ng/ml, activins A and AB inhibited the increase approximately 30% and 10%, respectively, and at 25 ng/ml both activins produced almost maximal inhibition, i.e., approximately 40%. Activin B caused 10% inhibition at 12 ng/ml, and at 25 ng/ml produced almost maximal inhibition, approximately 30%. Further analysis with activin A indicated that the inhibition was caused by decreased HGF mRNA levels, followed by decreased cellular HGF levels. At 25 ng/ml, activin A inhibited the increase in HGF in the cellular lysate and the increase in HGF mRNA level approximately 80% and 40%, respectively. 相似文献
153.
Kazutaka Hirakawa Shinji Oikawa Yusuke Hiraku Iwao Hirosawa Shosuke Kawanishi 《Chemical research in toxicology》2002,15(1):76-82
We examined the redox properties of the "carcinogenic" catechol and the "noncarcinogenic" hydroquinone in relation to different DNA damaging activities and carcinogenicity using 32P-labeled DNA fragments obtained from the human genes. In the presence of endogenous NADH and Cu2+, catechol induces stronger DNA damage than hydroquinone, although the magnitudes of their DNA damaging activities were reversed in the absence of NADH. In both cases, DNA damage resulted from base modification at guanine and thymine residues in addition to strand breakage induced by Cu+ and H2O2, generated during the oxidation of catechol and hydroquinone into 1,2-benzoquinone and 1,4-benzoquinone, respectively. EPR and 1H NMR studies indicated that 1,2-benzoquinone is converted directly into catechol through a nonenzymatic two-electron reduction by NADH whereas 1,4-benzoquinone is reduced into hydroquinone through a semiquinone radical intermediate through two cycles of one-electron reduction. The reduction of 1,2-benzoquinone by NADH proceeds more rapidly than that of 1,4-benzoquinone. This study demonstrates that the rapid 1,2-benzoquinone two-electron reduction accelerates the redox reaction turnover between catechol and 1,2-benzoquinone, resulting in the enhancement of DNA damage. These results suggest that the differences in NADH-mediated redox properties of catechol and hydroquinone contribute to their different carcinogenicities. 相似文献
154.
Morikawa T Matsuda H Toguchida I Ueda K Yoshikawa M 《Journal of natural products》2002,65(10):1468-1474
The 80% aqueous acetone extract and the ethyl acetate-soluble portion from the dried fruit of Alpinia oxyphylla MIQUEL were found to show inhibitory effects on nitric oxide production in lipopolysaccharide-activated macrophages and antigen-induced degranulation in RBL-2H3 cells. A new eudesmane-type sesquiterpene, oxyphyllol A, and two eremophilane-type sesquiterpenes, oxyphyllols B and C, were isolated from the ethyl acetate-soluble portion, together with 16 known constituents. The absolute stereostructures of oxyphyllols A, B, and C were determined on the basis of chemical and physicochemical evidence. The effects of isolated components on nitric oxide production were examined, and nine constituents including oxyphyllol A and nootkatone were found to show inhibitory activity. On the other hand, five constituents inhibited the release of beta-hexosaminidase from RBL-2H3 cells. 相似文献
155.
Keishi Maruo Tetsu Nagata Satoshi Yamamoto Kaoru Nagai Yukio Yajima Soji Maruo Tomoyuki Nishizaki 《Brain research》2003,977(2):294
In a whole-cell patch-clamp configuration, currents through N-methyl-
-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels were monitored in cultured rat hippocampal neurons, and those currents were depressed to 25 and 28% of basal levels, respectively, by 3-min treatment with tunicamycin (10 μM), an inhibitor of protein N-glycosylation. Tunicamycin (10 μM) reduced amplitude of population spikes elicited in the dentate gyrus of rat hippocampal slices, reaching 78% of basal levels 60 min after the beginning of treatment, and long-term potentiation (LTP) of the perforant path was never induced in the presence of tunicamycin. Tunicamycin, thus, appears to serve as a modulator for NMDA and AMPA receptors, regardless of N-glycosylation, thereby inhibiting neurotransmission and LTP in the dentate gyrus. 相似文献
156.
Sugawara T Sato M Itoi K Sugawara A Matsuda Y Shimada K Sado T Wu S Kondo T 《The Journal of thoracic and cardiovascular surgery》2002,124(6):1237-1238
157.
Role of hypomagnesemia in chronic cyclosporine nephropathy 总被引:4,自引:0,他引:4
Miura K Nakatani T Asai T Yamanaka S Tamada S Tashiro K Kim S Okamura M Iwao H 《Transplantation》2002,73(3):340-347
BACKGROUND: Hypomagnesemia is a common finding of cyclosporine (CsA)-treated patients and has been proposed as both a cause and a consequence of CsA-induced nephrotoxicity. This experiment was conducted to elucidate the role of hypomagnesemia in the pathogenesis of chronic CsA nephropathy. METHODS: CsA (15 mg/kg/day subcutaneously) was administered to rats maintained on a low-sodium diet for 1, 2, and 4 weeks, and the effects of magnesium (Mg) supplementation on renal function, renal histology, and renal gene expression profile of fibrogenic molecules and vasoconstrictors was examined. RESULTS: CsA elicited hypomagnesemia and induced a progressive decline in glomerular filtration. At 28 day, renal tubular atrophy and cortical striped interstitial fibrosis were evident with CsA treatment. Dietary supplementation of Mg ameliorated CsA-induced hypomagnesemia and almost completely abolished CsA-induced chronic fibrotic lesions. Neither CsA nor Mg supplementation affected blood pressure. Renal cortical mRNA of transforming growth factor beta, plasminogen activator inhibitor (PAI)-1, and extracellular matrix started to increase at 14 days and elevated further at 28 days. In contrast, the increase in mRNA of tissue inhibitor of matrix metalloproteinase-1 and renin was evident early at 7 days and reached peak at 14 days. These mRNA increases, except that of renin, were almost abolished when hypomagnesemia was corrected. Magnesium supplementation also improved glomerular dysfunction, at least in part, through inhibition of up-regulated mRNA of endothelin-1. CONCLUSION: CsA-induced hypomagnesemia contributes to chronic renal fibrotic lesions seen during CsA treatment through up-regulation of fibrogenic molecules, most notably early activation of tissue inhibitor of matrix metalloproteinase-1 expression. 相似文献
158.
Ishii N Yonese J Tsukamoto T Maezawa T Fukui I Ishikawa Y Aoki N 《Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology》2002,93(5):642-647
A 65-year-old housewife presented with a diagnosis of malignant spindle cell tumor of the bladder which had been diagnosed by work up for chance hematuria. Urine cytology revealed a small number of squamous epithelial cells showing dyskeratosis but no spindle cells. Computed tomography and magnetic resonance images showed a markedly enhanced mass, 4 cm in diameter, on the anterior wall of the urinary bladder, which appeared to be adhesive to the pubic bone. However, no metastasis was found. Under the suspicion of sarcoma of the urinary bladder, we performed anterior pelvic exenteration with construction of an ileal conduit. Although the anterior wall of the urinary bladder was mildly adhesive to the pubic bone, the surgical margin was negative for malignant cells. The tumor corresponded to a fibrosarcoma that infiltrated the adipose tissue surrounding the urinary bladder. The entire mucosa of the bladder showed diffuse squamous metaplasia, and well differentiated squamous cell carcinoma with pearl formation was found in part. These two malignant tumors were clearly apart from each other, resulting in the histologic diagnosis of synchronous multiple malignant tumors of the bladder. The patient developed a local relapse and pulmonary metastasis of fibrosarcoma one month postoperatively and died two month later without any response to chemotherapy (CYVADIC) and radiotherapy. The current case seems to be the first one in Japan (third in the world) of a patient with multiple synchronous primary malignant tumors, carcinoma and sarcoma, airsing in the urinary bladder. 相似文献
159.
160.
Abnormalities of rate-corrected QT intervals in Parkinson's disease-a comparison with multiple system atrophy and progressive supranuclear palsy 总被引:4,自引:0,他引:4
Deguchi K Sasaki I Tsukaguchi M Kamoda M Touge T Takeuchi H Kuriyama S 《Journal of the neurological sciences》2002,199(1-2):31-37
A number of patients with Parkinson's disease (PD) and multiple system atrophy (MSA), in whom sudden death does occur occasionally, have QT or rate-corrected QT (QTc) interval prolongation on electrocardiogram (ECG). Although these QT or QTc interval abnormalities are likely related to autonomic dysfunction, the pathophysiology remains unknown. The aim of this study was to compare the degree of QTc interval prolongation among akinetic-rigid syndromes, namely PD and related disorders, and to evaluate the relationship between QTc prolongation and severity of autonomic dysfunction. Thirty-four patients with PD, 22 with MSA, 11 with progressive supranuclear palsy (PSP) and 30 healthy controls underwent standard autonomic function tests, and electrocardiography variables (RR, QT and QTc intervals) were measured by an ECG recorder with an automated analyzer. The relationship between QTc interval and cardiovascular reflex tests were also analyzed. Orthostatic hypotension and decreased heart rate in response to respiratory stimuli were prominent in MSA, while these were relatively mild in PD. Unlike the RR and QT intervals, the QTc interval significantly differed among all groups (p<0.01). The QTc interval was significantly prolonged in PD (409+/-17 ms; p<0.001) and MSA (404+/-14 ms; p<0.05) compared with healthy controls (394+/-19 ms). Neither autonomic dysfunction nor QTc interval prolongation was evident in PSP. QTc intervals and cardiovascular reflexes did not correlate, except for Valsalva ratio. The QTc interval was obviously prolonged in PD patients to an extent that could not be accounted for simply by autonomic dysfunction levels. MSA patients showed slightly prolonged QTc intervals in spite of marked cardiovascular autonomic dysfunction. Abnormalities of the QTc may reflect the degeneration of cardioselective sympathetic and parasympathetic neurons that cannot be fully captured by cardiovascular autonomic function tests. 相似文献