全文获取类型
收费全文 | 2448篇 |
免费 | 115篇 |
国内免费 | 20篇 |
专业分类
耳鼻咽喉 | 54篇 |
儿科学 | 31篇 |
妇产科学 | 13篇 |
基础医学 | 378篇 |
口腔科学 | 41篇 |
临床医学 | 119篇 |
内科学 | 662篇 |
皮肤病学 | 67篇 |
神经病学 | 144篇 |
特种医学 | 72篇 |
外科学 | 438篇 |
综合类 | 2篇 |
预防医学 | 50篇 |
眼科学 | 38篇 |
药学 | 124篇 |
中国医学 | 4篇 |
肿瘤学 | 346篇 |
出版年
2023年 | 18篇 |
2022年 | 27篇 |
2021年 | 59篇 |
2020年 | 25篇 |
2019年 | 37篇 |
2018年 | 48篇 |
2017年 | 54篇 |
2016年 | 53篇 |
2015年 | 59篇 |
2014年 | 77篇 |
2013年 | 78篇 |
2012年 | 130篇 |
2011年 | 133篇 |
2010年 | 85篇 |
2009年 | 76篇 |
2008年 | 146篇 |
2007年 | 163篇 |
2006年 | 140篇 |
2005年 | 175篇 |
2004年 | 175篇 |
2003年 | 177篇 |
2002年 | 181篇 |
2001年 | 21篇 |
2000年 | 10篇 |
1999年 | 31篇 |
1998年 | 42篇 |
1997年 | 40篇 |
1996年 | 32篇 |
1995年 | 26篇 |
1994年 | 19篇 |
1993年 | 21篇 |
1992年 | 27篇 |
1991年 | 17篇 |
1990年 | 10篇 |
1989年 | 23篇 |
1988年 | 17篇 |
1987年 | 11篇 |
1986年 | 12篇 |
1985年 | 11篇 |
1984年 | 9篇 |
1983年 | 18篇 |
1982年 | 10篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1975年 | 3篇 |
1973年 | 3篇 |
1969年 | 3篇 |
1962年 | 2篇 |
排序方式: 共有2583条查询结果,搜索用时 15 毫秒
21.
Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism 总被引:16,自引:0,他引:16 下载免费PDF全文
Chen J Zhao S Nakada K Kuge Y Tamaki N Okada F Wang J Shindo M Higashino F Takeda K Asaka M Katoh H Sugiyama T Hosokawa M Kobayashi M 《The American journal of pathology》2003,162(4):1283-1291
In the tumor cells exposed to hypoxia, hypoxia-inducible factor-1 (HIF-1)-mediated adaptation responses such as angiogenesis and anaerobic metabolism are induced for their survival. We have recently reported that the constitutive expression of HIF-1 alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and glucose deprivation. We then established dominant-negative HIF-1 alpha (dnHIF-1 alpha) transfectants and examined their susceptibility to apoptosis and growth inhibition induced by hypoxia and glucose deprivation in vitro and their tumorigenicity in SCID mice. We further examined the expressions of aldolase A and Glut-1 in vitro and Glut-1 expression and glucose uptake in the tumor tissues and microvessel counts in the tumor tissues. As a result, dnHIF-1 alpha rendered the pancreatic cancer cells sensitive to apoptosis and growth inhibition induced by hypoxia and glucose deprivation. Also it abrogated the enhanced expression of Glut-1 and aldolase A mRNAs under hypoxia and reduced the expression of Glut-1 and the glucose uptake in the tumor tissues and consequently in vivo tumorigenicity. We found no significant difference in the microvessel counts among the tumor tissues. From these results, we suggest that the disruption of the HIF-1 pathway might be effective in the treatment of pancreatic cancers. 相似文献
22.
Isao Katayama Masaki Shimizu Myota Miura Masanobu Maruyama Masayuki Kobayashi Yuuichi Iino Masaru Izuo Susumu Wakatsuki 《Virchows Archiv : an international journal of pathology》1984,402(4):353-359
Summary In a study of 277 patients with breast carcinomas, the PAP immunoperoxidase method for demonstrating endogenous estrogen was correlated with the sucrose density gradient (SDG) assay and with histologic and clinical features. The results from the PAP method and SDG assay agreed in 59 of 84 patients (82.1%) on whom both methods were performed. Histologically, the PAP method was positive in 7 of 7 patients with non-invasive carcinomas, in 164 of 233 patients (70.4%) with common invasive ductal carcinoma, and in 21 of 22 of those with special histological types of invasive carcinomas not including Paget's disease, medullary or apocrine carcinoma, where only 5 of 14 were positive. Clinically, 15 of 18 patients with positive endogenous estrogen showed a response to endocrine therapy as opposed to 1 of 9 patients with a negative endogenous estrogen. The mean survival was 31.2 and 15.6 months, respectively for patients with positive and negative endogenous estrogen. Remission for longer than 2 years was seen more often in patients with positive endogenous estrogen. These results suggest a clinical utility of the present PAP method which, therefore, deserves a further trial as an alternative to histochemical methods aiming at the estrogen receptors.This work was supported by Grants-in Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (No. 56480119).This paper was presented at the 72nd Annual Meeding of International Academy of Pathology (United States-Canadian Division), Atlanta, Georgia, March 1, 1983. 相似文献
23.
Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET) 总被引:2,自引:2,他引:0
John M. Bolster Willem Vaalburg Anne M. J. Paans Theo H. van Dijk Philip H. Elsinga Jan B. Zijlstra Do A. Piers Nanno H. Mulder Martien G. Woldring Hans Wynberg 《European journal of nuclear medicine and molecular imaging》1986,12(7):321-324
To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-11C)-tyrosine by 11C-carboxylation of the appropriate -lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-11C)-Tyrosine in 0.1 N NaH2PO4 buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-11C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-11C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma. 相似文献
24.
Oral senile amyloidosis in senescence accelerated mouse (SAM) was examined for two SAM sublines (P/2/Iw and R/1/Iw) and for various ages by light microscopy, immunohistochemistry, and electron microscopy. The amyloid deposition, identified by green birefrigence following Congo red stain, was observed only in P/2/Iw. In P/2/Iw, no amyloid deposition was found at age 6 months; however, frequency and extent of such deposits increased with advancing age. Distribution of amyloid deposition was as follows: along papillary layers of mucous epithelium in the tongue, the gingiva, the palate, and the buccal mucosa; foci in connective tissues; along vessels, muscles, and minor salivary glands. Immunohistochemically, the amyloid deposition was positive with anti-ASSAM serum being raised against a unique amyloid protein ASSAM which probably induced "senile systemic amyloidosis". P/2/Iw is useful as an animal model of oral senile amyloidosis. 相似文献
25.
Shigeru Fujimoto Makoto Takahashi Kokuriki Kobayashi Masanobu Kure Hiroshi Masaoka Haruo Ohkubo Shigeo Isaka Jun Shimazaki 《Surgery today》1993,23(12):1094-1098
A huge rectosigmoidal cancer which extended into the urinary bladder in a 64-year-old man is herein described. The tumor occupied the pelvic and lower abdominal cavities, while the rectosigmoid was totally obstructed. No hepatic or pulmonary metastasis was evident. The ventral and flank sides of the peritoneum in the right lower abdomen, right common iliac vessels, bilateral ureters, terminal ileum, cecum, ascending colon, and urinary bladder were all directly invaded by the tumor, but the aorta, sacrum, and lower rectum were free of cancer. Consequently, an anterior pelvic exenteration was carried out along with an ileal conduit and a right hemicolectomy. Immediately after the exenteration, intra-pelvic hyperthermochemotherapy was performed using a 46–47°C perfusate containing 40 g/ml of mitomycin C (MMC) and 200 g/ml of cisplatin (CDDP), for 90 min, in an attempt to prevent any further local recurrence. A right hemicolectomy and a permanent colostomy were done simultaneously with the hyperthermia treatment. After an uneventful postoperative course, the patient was prescribed adjuvant chemotherapy, i.e., two administrations of 17 mg/m2 and 21 mg/m2 of MMC, and ten doses of 710 mg/m2 of 5-fluorouracil (5-FU) followed by five doses of 535 mg/m2 of 5-FU. At the time of this writing, the patient is still alive without recurrence at 21 months after surgery. 相似文献
26.
Shuji Kaneko Nobumichi Yada Koichiro Fukuda Masanobu Kikuwaka Akinori Akaike Masamichi Satoh 《British journal of pharmacology》1997,121(4):806-812
- Desensitization of μ- and κ-opioid receptor-mediated inhibition of voltage-dependent Ca2+ channels was studied in a Xenopus oocyte translation system.
- In the oocytes coexpressing κ-opioid receptors with N- or Q-type Ca2+ channel α1 and β subunits, the κ-agonist, U50488H, inhibited both neuronal Ca2+ channel current responses in a pertussis toxin-sensitive manner and the inhibition was reduced by prolonged agonist exposure.
- More than 10 min was required to halve the inhibition of Q-type channels by the κ-agonist. However, the half-life for the inhibition of N-type channels was only 6±1 min. In addition, in the oocytes coexpressing μ-opioid receptors with N-type or Q-type channels, the uncoupling rate of the μ-receptor-mediated inhibition of N-channels was also faster than that of Q-type channels.
- In the oocytes coexpressing both μ- and κ-receptors with N-type channels, stimulation of either receptor resulted in a cross-desensitization of the subsequent response to the other agonist. Treatment of oocytes with either H-8 (100 μM), staurosporine (400 nM), okadaic acid (200 nM), phorbol myristate acetate (5 nM) or forskolin (50 μM) plus phosphodiesterase inhibitor did not affect either the desensitization or the agonist-evoked inhibition of Ca2+ channels.
- These results suggest that the rate of rapid desensitization is dependent on the α1 subtype of the neuronal Ca2+ channel, and that a common phosphorylation-independent mechanism underlies the heterologous desensitization between opioid receptor subtypes.
27.
Tomoaki Yuhi Akihiko Wada Ryuichi Yamamoto Masanobu Urabe Hiromi Niina Futoshi Izumi Toshihiko Yanagital 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(2):209-212
We have previously reported that in bovine adrenal chromaffin cells Ptychodiscus brevis toxin-3 (PbTx-3) does not alter the veratridine-induced 22Na influx when given alone, but increases the influx of 22Na when co-applied with either - or -scorpion venom (Wada et al. 1992). In the present study, we characterized [3H]PbTx-3 binding in bovine adrenal chromaffin cells. [3H]PbTx-3 binding was saturable, reversible and of high-affinity with an equilibrium dissociation constant (Kd) of 32.0±4.9 nmol/1 and a maximum binding capacity Bmax of 6.2 ± 1.2 pmol/4 × 106 cells (4.5 ± 0.9 pmol/mg cell protein). A Hill plot revealed the lack of cooperative interaction among the binding sites. Unlabelled PbTx-3 inhibited [3H]PbTx-3 binding with an IC50 of 31 nmol/l. However, tetrodotoxin, veratridine, - and -scorpion venom, or veratridine in combination with either - or -scorpion venom did not alter [3H]PbTx-3 binding. All these results suggest that PbTx-3 binds to a site (site 5) distinct from the previously known four toxin binding sites, which does not gate voltage-dependent Na channels by itself, but is specifically involved in the allosteric modulation of Na channels in adrenal medullary cells.
Correspondence to: A. Wada at the above address 相似文献
28.
The gravity model, a method for analyzing transportation distribution in transportation engineering, was used to explain patient
trips between ten health service regions in a Japanese prefecture. The OD (Origin-Destination) tables were constructed with
zoning by regions, distinguishing between out- and inpatients. The observed trips were determined from the data of a survey
conducted in 1992 that reported the locations of patient residences and chosen medical facilities.
The base values used in the model calculations were the population size of each region and the road distance between the centers
of regions. Problems of intrazonal trip were avoided by setting a mean intrazonal movement distance.
This model was calibrated by the linear regression method with simultaneous validation by the index of correlation coefficients.
The model was found to accurately simulate the effect of distance on the choice of medical facilities and the differences
between the characteristics of in- and out-patients. The population value in use showed the relation not only with demand
but also the supply of clinical services. It was suggested that the model presented here was useful in the allocation of medical
resources and would help explain the relationship between suppliers and consumers of medical services. 相似文献
29.
30.
Immunolocalization of basic fibroblast growth factor during wound repair in rat retina after laser photocoagulation 总被引:3,自引:0,他引:3
Chikako Yamamoto Nahoko Ogata Xianjin Yi Kanji Takahashi Miki Miyashiro Haruhiko Yamada Masanobu Uyama Kouichi Matsuzaki 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1996,234(11):695-702
Background: Basic fibroblast growth factor (bFGF) stimulates the mitogenesis of various cells and plays a key role in wound repair. We studied the immunohistochemical localization of bFGF during wound repair in the rat retina after laser photocoagulation. Methods: Krypton laser photocoagulation was performed on the eyes of pigmented rats. The eyes were enucleated on days 1, 3, 7, 14 and 28 after the photocoagulation, and the immunohistochemical localization of bFGF was assessed. Two different monoclonal antibodies and one polyclonal antibody against bFGF as first antibodies were used. Results: Marked immunoreactivity for bFGF was found in the ganglion cell layer, and weak immunoreactivity for bFGF was found in the retinal pigment epithelial (RPE) cells of the normal adult rat retina. On day 3 after laser photocoagulation, the nuclei and cytoplasm of proliferating RPE cells at the center of the photocoagulated lesion showed intense bFGF immunoreactivity. The nuclei of RPE cells around the lesion showed intense bFGF immunoreactivity. Macrophages that migrated into the lesion showed positive staining for bFGF. These immunoreactivity decreased with time. Controls (0.05 M Tris-HCl buffer, normal serum, or these same antibodies preabsorbed with bFGF) did not show positive staining. Conclusion: The finding of an elevated expression of bFGF immunoreactivity in the photocoagulated lesion suggests that bFGF may play a role in wound repair in the rat retina after laser photocoagulation. 相似文献