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101.
Csillik A Knyihár E Okuno E Krisztin-Péva B Csillik B Vécsei L 《Experimental neurology》2002,177(1):233-241
Activation of excitatory amino acid receptors by endogenous excitotoxins results in degenerative changes characteristic of neurodegenerative brain diseases such as Huntington's disease. Excitatory amino acid receptors are present in the highest concentration in the striatum, the hippocampal region, and the temporal lobe. The most potent, naturally occurring excitatory amino acid receptor antagonist is kynurenic acid (KYNA) which acts preferentially on N-methyl-D-aspartate (NMDA) receptors. KYNA is produced from L-kynurenine, by the action of the enzymes kynurenine aminotransferases (KAT I and KAT II). Several inhibitors of mitochondrial energy metabolism result in an indirect excitotoxic neuronal degeneration. We examined whether systemic administration of the mitochondrial toxin 3-nitroproprionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, which also acts by an indirect excitotoxic mechanism, would produce alterations in the immunohistochemical pattern of KAT I. Our present investigations demonstrate that after 15 days of administration of 3-NP, an inhibitor of mitochondrial Complex II, the most severe depletion of KAT I occurred in the striatum; less severe depletion occurred in other brain areas investigated, following a striatum > hippocampus > temporal cortex gradient. The alterations induced by 15 days of 3-NP treatment were less conspicuous in 6-week-old (young) animals than in 3-month-old adults. In these adult animals, 3-NP induced necrotic cores in the striatum, characterized by destruction of neuronal and glial elements, similar to that seen in the histologic and neurochemical features of Huntington's disease. It appears that immunohistochemical depletion of KAT after administration of 3-NP to adult animals may contribute to the pathological processes that characterize Huntington's disease. 相似文献
102.
Synergistic induction of apoptosis by acyclic retinoid and interferon-beta in human hepatocellular carcinoma cells 总被引:5,自引:0,他引:5
Obora A Shiratori Y Okuno M Adachi S Takano Y Matsushima-Nishiwaki R Yasuda I Yamada Y Akita K Sano T Shimada J Kojima S Okano Y Friedman SL Moriwaki H 《Hepatology (Baltimore, Md.)》2002,36(5):1115-1124
Acyclic retinoid, a synthetic retinoid analog, as well as interferon alfa (IFN-alpha) and IFN-beta induce apoptosis in hepatocellular carcinoma (HCC) cells and are used clinically in the prevention of HCC. Here, we show that acyclic retinoid acts synergistically with IFNs in suppressing the growth and inducing apoptosis (as characterized by DNA fragmentation and chromatin condensation) in 5 human HCC cell lines (JHH7, HuH7, PLC/PRF/5, HLE, and HLF). This synergism was only observed when cells were pretreated with the acyclic retinoid, whereas natural retinoic acids (all-trans and 9-cis retinoic acid) were ineffective. This promotion may be due to up-regulation of type 1 IFN receptor (IFNR) expression by the retinoid. Accordingly, incubation with antitype 1 IFNR antibody abolished the synergy. Enhanced IFNR expression was accompanied by increased expression and DNA-binding activity of STAT1, an intracellular signal transducing molecule of IFNR, and increased induction of 2', 5'-oligoadenyl-5'-triphosphate synthetase, which is a target gene of STAT1. Acyclic retinoid did not have any effects on the growth of normal human hepatocytes (Hc) probably because of a lack of IFNR and STAT1 up-regulation. In conclusion, these results provide a rationale for combined biochemoprevention of HCC using acyclic retinoid and IFN-beta. 相似文献
103.
目的 探讨复治肺结核病人形成原因。方法 使用调查表的方法 ,对前来诊治的复治涂阳肺结核病人的首次诊疗 ,管理情况进行问卷调查。结果 综合医院仍然为大多数患者的首次诊疗单位 ,因此部分肺结核患者未能得到正确的诊断、治疗和化疗管理。导致 67.2 %病人“中断”或“间断”治疗 ;另外结核病健康教育宣传做得不够 ,60 .3 %的患者诊断前未接受过防痨宣教 ,3 4.5 %的患者接受初次化疗时仍未得到宣教。这些均在导致复治病人的产生中起了重要作用。结论 加大DOTS覆盖面 ,加强归口管理力度 ,做好防治结核病教育工作是防止复治肺结核病人产生的重要环节。 相似文献
104.
105.
Okuno S Hamada H Yasuoka M Watanabe H Fujiki Y Yamada N Sohda S Kubo T 《The journal of obstetrics and gynaecology research》1999,25(6):407-410
OBJECTIVE: Our purpose was to evaluate plasma levels of brain natriuretic peptide (pBNP) and cyclic guanosine monophosphate (pcGMP) in preeclamptic patients and controls. STUDY DESIGN: Blood samples were obtained from 35 patients with preeclampsia and from the same women during the subsequent puerperal period. The control group consisted of normotensive pregnant women, matched with the patients for age, gestational age, and parity. The concentrations of pBNP and pcGMP were determined by the RIA method. Statistical analysis was performed using the Mann-Whitney's U test. RESULTS: The pBNP level in the preeclampsia group was significantly increased, to 7-fold that of the control group. The pcGMP level was 50% higher in the preeclampsia group than in the control group, but this was not significant. Both the pBNP level and the pcGMP level in the puerperal period did not significantly differ between the patients and the controls. CONCLUSION: The pBNP concentrations increased in the preeclamptic women, and then these compensations were normalized in the puerperal period. 相似文献
106.
Z Iwasa M Yamamoto A Tanaka K Okuno N Sagara T Matsuda T Fukuhara M Yasutomi 《Gan no rinsho》1985,31(15):1865-1870
A comparative study of rat and human mammary tumors was undertaken to clarify the mechanism of hormone dependency by the PAP method. In normal mammary glands, histological estrogen receptor ER (+) cells were observed in the ductal epithelium and acinal cells, while only ER (-) cells were noted in HAN. After overiectomy, 55.6% of the ER (+) cells changes to ER (-). Furthermore, histological changes were glandular atrophy, anaplastic changes, (with) the remaining ER (+) cells (being in the) insular group. Those ER (+) cancer cells seem to be different in hormone sensitivity. As for human mammary glands, proliferation of ER (+) cells was observed in papillary lesions as duct papillomatosis. In the cancer tissues as a whole, ER (+) and ER (-) cancer cells were mixed, showing a so-called mosaic pattern. 相似文献
107.
108.
109.
The effect of paraoxon, a microsomal deacetylase inhibitor, on the mutant genicity of 2-acetylaminofluorene (AAF) by liver homogenates was compared between the AAF carcinogenesis-resistant guinea pigs and the susceptible mice and rats. The mutagenicity of AAF was mostly abolished by paraoxon, not only in the 3 kinds of untreated animals but also in guinea pigs treated with a combination of phenobarbital and 5,6-benzoflavone, whereas about 50% of the mutagenicity was resistant to paraoxon in treated mice and rats. We suggest that microsomal deacetylase activity is crucially involved in the mutagenic activation of AAF by guinea pig liver homogenates, while the enzyme activity other than the deacetylase activity is also important in the activation by liver homogenates from treated mice or rats. 相似文献
110.
Kurosaka S Irie A Mizoguchi H Okuno N Iwabuchi K Baba S 《International journal of clinical oncology / Japan Society of Clinical Oncology》2005,10(5):362-365
A 52-year-old woman was referred to our institute for the evaluation of a tumor in her pelvic cavity. The tumor seemed to
have arisen from the bladder or urethra, and bilateral iliac lymphadenopathy was seen. Her urethral mucosa looked intact according
to the results of cystourethroscopy. Histopathological examination of the biopsy specimens showed clear-cell adenocarcinoma.
She underwent radical cystourethrectomy with complete pelvic lymph node dissection and the construction of a bilateral ureterocutaneostomy.
Macroscopically, the tumor had arisen from the trigone of the bladder, and histopathological examination of the tumor revealed
adenocarcinoma exhibiting solid clear cells with glandular and papillary patterns. The tumor had infiltrated perivesical structure
(pT3a), and metastases in multiple pelvic lymph nodes were recognized (pN3). Postoperatively, three courses of systemic combination
chemotherapy with 5-fluouracil (FU) and cisplatin, along with a total of 45 Gy of irradiation during the second course of
chemotherapy, were conducted. No evidence of the disease has been seen 28 months after the surgery. 相似文献