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91.
Reduced MLH1 expression after chemotherapy is an indicator for poor prognosis in esophageal cancers.
Kentaro Kishi Yuichiro Doki Masahiko Yano Takushi Yasuda Yoshiyuki Fujiwara Syuji Takiguchi Sontae Kim Ichiro Higuchi Morito Monden 《Clinical cancer research》2003,9(12):4368-4375
PURPOSE: Loss of function or expression of the mismatch repair gene MLH1 has been implicated in experimentally acquired resistance to cisplatin (CDDP) and other anticancer agents. The clinical significance of MLH1 expression was evaluated in advanced thoracic squamous cell carcinoma of the esophagus (ESCC) treated by neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: We investigated MLH1 and P53 expression by immunohistochemistry in the surgical specimens of 107 patients who had undergone preoperative chemotherapy using CDDP along with 5-FU and ADM. These findings were correlated with the clinical outcome for this treatment. Biopsy samples before chemotherapy in 20 of these patients, and another 43 surgical specimens without chemotherapy, were also examined as control samples. RESULTS: In surgical specimens of ESCC, low MLH1 expression was not frequent without chemotherapy, whereas it was commonly observed after chemotherapy (14 versus 37%, P = 0.0057). Comparison between samples before and after chemotherapy revealed that MLH1 expression was unchanged during chemotherapy in 12 of 20 patients (60%) but was from high to low in 8 of 20 patients (40%). In the surgical specimen after neoadjuvant chemotherapy, MLH1 expression was not correlated with any clinicopathological factors, including the response to chemotherapy. However, low MLH1 showed poorer prognosis than high MLH1 (5-year survival 40.6 versus 19.3%, P = 0.0393), and in multivariate analysis, MLH1 was an independent prognostic factor for this multimodal treatment, following lymph node metastasis and clinical response to chemotherapy. Positive p53 expression, which was not affected by chemotherapy, was weakly associated with a poor response and clinical outcome, although this trend was not significant. CONCLUSIONS: In advanced ESCC, expression of MLH1 is reduced during CDDP-based chemotherapy, and this may partly account for poor postoperative survival. 相似文献
92.
Homotypic Adhesion through Carcinoembryonic Antigen Plays a Role in Hepatic Metastasis Development 总被引:2,自引:0,他引:2
Toshiaki Yoshioka Takashi Masuko Hitoshi Kotanagi Osamu Aizawa Yuri Saito Hiroshi Nakazato Kenji Koyama Yoshiyuki Hashimoto 《Cancer science》1998,89(2):177-185
We established a cell line with high metastatic potential to the liver (LS-LM4) after four successive repetitions of splenic injection of liver-metastatic cells in SCID mice. This cell line strongly expressed CEA and showed increased homotypic adhesion as compared with the parent cell line (LS174T). To examine the role of CEA in the increased homotypic adhesion, LS-LM4 cells were treated with anti-CEA antibody and subjected to an in vitro adhesion and aggregation assay. Further, to study the role of CEA in the hepatic metastasis of cells with high metastatic potential, LS-LM4 cells were treated with anti-CEA antibody, and the inhibition of hepatic metastasis after splenic injection in vivo was examined. There was a 62% decrease in the homotypic adhesion of anti-CEA antibody-treated (100 μg/ml) LS-LM4 cells under a Ca2+ -free condition as compared with the control ( P <0.01). Anti-CEA antibody (100 μg/ml) inhibited cell aggregation under a Ca2+ -free condition ( P <0.05). Treatment with anti-E-cadherin antibody (60 μ/ml) plus anti-CEA antibody (100 μg/ml) inhibited cell aggregation more potently than anti-E-cadherin antibody treatment alone in the presence of Ca2+ . In vivo , there was a 75% decrease in the number of hepatic metastatic nodules in the G125 anti-CEA antibody-treated group as compared with the control group ( P <0.01). Similarly, there was a 40% decrease in the diameter of metastatic nodules and there was a 90% decrease in total tumor volume of hepatic metastasis in the G125 anti-CEA antibody-treated group as compared with the control ( P <0.01). These results suggest that increased metastatic potential to the liver is at least partly due to increased homotypic binding mediated by CEA. 相似文献
93.
Absence of p53 Overexpression and Favorable Response to Cisplatin-based Neoadjuvant Chemotherapy in Urothelial Carcinomas 总被引:3,自引:0,他引:3
Yoshiyuki Kakehi Enver Özdemir Tomonori Habuchi Hirohiko Yamabe Takayuki Hashimura Yoshitaka Katsura Osamu Yoshida 《Cancer science》1998,89(2):214-220
It has been controversial whether cancer cells harboring loss or inactivation of the tumor suppressor p53 are resistant or sensitive to DNA-damaging agents including cisplatin and doxorubicin. Overexpression of mdm2 oncoprotein, a negative regulator of p53, is assumed to be an alternative to p53 dysfunction. Archival urothelial carcinoma specimens obtained from 60 patients prior to cisplatin-based chemotherapy were immunohistochemically studied for overexpression of p53 and mdm2. Thirty-two patients (group I) were treated with chemotherapy in the neoadjuvant setting, while 28 patients (group II) underwent chemotherapy for distant metastases or inoperable locoregional tumors. In group I, the responsiveness was correlated with staining status of p53 ( P =0.0225) and the combination of p53 and mdm2 ( P =0.0497). Negative staining of p53 and negative for both p53 and mdm2 could have predicted favorable response to chemotherapy in 16 of 18 (88.9%) and in 12 of 13 (92.3%) tumors, respectively. On the other hand, p53-positive and p53 and/or mdm2-positive staining could have predicted poor response only in 7 of 14 (50.0%) and 8 of 19 (42.1%) tumors, respectively. Disease-specific survival of the p53-negative group was significantly superior to that of the p53-positive group ( P =0.0086). Difference in survival did not become more significant when overexpression of mdm2 was taken into consideration ( P =0.0456). In contrast, in group II, there was no correlation of responsiveness to chemotherapy or survival with p53- or p53/mdm2-staining status. The patients with urothelial carcinomas negative for overexpression of p53 will benefit from neoadjuvant chemotherapy. From clinical viewpoint, however, p53 status alone or the combination of p53 and mdm2 status is not enough to identify those patients who will not benefit from the treatment. 相似文献
94.
Tetsuya Shirokawa Yoshiyuki Ishida Wataru Matsunaga Sadamu Nakai Ken-ichi Isobe 《Nihon shinkei seishin yakurigaku zasshi》2005,25(1):43-48
The locus coeruleus (LC), located within the caudal pontine central gray, is composed of noradrenaline-containing neurons. The axons of these neurons form extensive collateral branches that project widely to many brain sites. The function of the LC is still unclear at present, however, LC neurons are known to exhibit marked axonal regeneration and sprouting in response to brain damage. We investigated the age-related changes in noradrenergic innervations of the frontal cortex, using in vivo electrophysiological techniques and immunohistochemistry. While noradrenergic innervations gradually decreased with age in the frontal cortex, a high degree of sprouting occurred in the LC axon terminals in middle age. Neither the electrophysiological properties of LC neurons nor NA levels in the frontal cortex changed with age. These findings suggested that the LC neurons preserve a strong capacity to remodel their axon terminals even in the aging brain. Exogenous brain-derived neurotrophic factor (BDNF) infusion caused a marked increase in the density of noradrenergic axon in the aged brain, but no trophic action of BDNF was observed in the young or middle-aged brain. The result suggests that BDNF is necessary for the maintenance of noradrenergic innervations in the aged brain. 相似文献
95.
Wang L Kuroiwa Y Kamitani T Li M Takahashi T Suzuki Y Shimamura M Hasegawa O 《Journal of neurology》2000,247(5):356-363
To determine whether there are characteristic changes in event-related potentials (ERPs) in parkinsonian syndromes we studied
8 patients with progressive supranuclear palsy (PSP), 10 patients with corticobasal degeneration (CBD), 9 patients with striatonigral
degeneration (SND), and 16 patients with idiopathic Parkinson's disease (PD) with a mean duration of illness shorter than
5 years in each group. A visual oddball paradigm was employed to elicit P300. P300 to the rare target and rare nontarget stimuli
and reaction time (RT) to rare target stimuli in each group were compared with those in the corresponding age-matched normal
control group and to each other after age correction. The correlation of P300 and RT to motor disability score was also studied.
In PSP P300 amplitude was markedly reduced while in CBD P300 latency was prolonged. P300 amplitude to rare nontargets in SND
and PD was attenuated. The mean RT in the PSP and the CBD group was significantly longer than in the other two groups. The
mean RT in PD and P300 amplitude to rare nontargets in both CBD and PD showed significant correlation with the severity of
motor disability. Simultaneous measurement of P300 and RT may yield useful supplementary information in facilitating diagnosis
of parkinsonian syndromes in addition to clinical criteria.
Received: 6 April 1999, Received in revised form: 5 August 1999, Accepted: 12 January 2000 相似文献
96.
The effects of conditioned fear on the release of noradrenaline in the hypothalamic paraventricular nucleus (PVN) and the involvement of corticotropin-releasing factor (CRF) receptor type 1 (CRFR1) in conditioned fear-induced changes in noradrenaline release were examined by intracerebral microdialysis in rats. Conditioned fear was produced by placing animals into a box where they had previously been exposed to a 5-min period of electric footshock, 135 min prior to the start of experiment. Conditioned fear for 20 min produced a significant increase in the release of noradrenaline in the PVN. Intraperitoneal preadministration of a selective nonpeptidic CRFR1 antagonist, CRA1000, completely blocked the conditioned fear-induced release of noradrenaline. These results suggest that CRFR1 is involved in the release of noradrenaline in the hypothalamic PVN induced by conditioned fear. 相似文献
97.
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
98.
Dihydropyrimidine dehydrogenase activity in 150 healthy Japanese volunteers and identification of novel mutations. 总被引:4,自引:0,他引:4
99.
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
100.
Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients
Na Cha Naoki Oshima Kenichi Kishimoto Satoshi Kotani Eiko Okimoto Tomotaka Yazaki Hiroki Sonoyama Akihiko Oka Yoshiyuki Mishima Kotaro Shibagaki Hiroshi Tobita Kousaku Kawashima Norihisa Ishimura Shunji Ishihara 《Journal of Clinical Biochemistry and Nutrition》2022,70(3):297
Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation. 相似文献