全文获取类型
收费全文 | 3283篇 |
免费 | 174篇 |
国内免费 | 25篇 |
专业分类
耳鼻咽喉 | 10篇 |
儿科学 | 132篇 |
妇产科学 | 16篇 |
基础医学 | 422篇 |
口腔科学 | 48篇 |
临床医学 | 169篇 |
内科学 | 876篇 |
皮肤病学 | 49篇 |
神经病学 | 301篇 |
特种医学 | 84篇 |
外科学 | 548篇 |
综合类 | 21篇 |
预防医学 | 71篇 |
眼科学 | 104篇 |
药学 | 231篇 |
中国医学 | 2篇 |
肿瘤学 | 398篇 |
出版年
2023年 | 16篇 |
2022年 | 47篇 |
2021年 | 64篇 |
2020年 | 46篇 |
2019年 | 46篇 |
2018年 | 69篇 |
2017年 | 55篇 |
2016年 | 62篇 |
2015年 | 63篇 |
2014年 | 84篇 |
2013年 | 122篇 |
2012年 | 200篇 |
2011年 | 207篇 |
2010年 | 108篇 |
2009年 | 95篇 |
2008年 | 173篇 |
2007年 | 224篇 |
2006年 | 214篇 |
2005年 | 207篇 |
2004年 | 203篇 |
2003年 | 191篇 |
2002年 | 207篇 |
2001年 | 48篇 |
2000年 | 39篇 |
1999年 | 54篇 |
1998年 | 43篇 |
1997年 | 40篇 |
1996年 | 46篇 |
1995年 | 29篇 |
1994年 | 32篇 |
1993年 | 42篇 |
1992年 | 28篇 |
1991年 | 29篇 |
1990年 | 35篇 |
1989年 | 33篇 |
1988年 | 19篇 |
1987年 | 20篇 |
1986年 | 30篇 |
1985年 | 21篇 |
1984年 | 18篇 |
1983年 | 13篇 |
1982年 | 14篇 |
1977年 | 10篇 |
1975年 | 8篇 |
1974年 | 16篇 |
1973年 | 14篇 |
1972年 | 8篇 |
1971年 | 10篇 |
1970年 | 8篇 |
1969年 | 8篇 |
排序方式: 共有3482条查询结果,搜索用时 15 毫秒
991.
Kiyoshi Takasuna Takehiro Hagiwara Masaaki Hirohashi Michiyuki Kato Mamoru Nomura Eiichi Nagai Tsuyoshi Yokoi Tetsuya Kamataki 《Cancer chemotherapy and pharmacology》1998,42(4):280-286
Purpose: SN-38, a metabolite of irinotecan hydrochloride (CPT-11), is considered to play a key role in the development of diarrhea
as well as in the antitumor activity of CPT-11. We have previously found that the inhibition of β-glucuronidase, which hydrolyzes
detoxified SN-38 (SN-38 glucuronide) to reform SN-38, in the lumen by eliminating the intestinal microflora with antibiotics,
markedly ameliorates the intestinal toxicity of CPT-11 in rats. In this study we compared the disposition of CPT-11 and its
metabolites in rats treated with and without antibiotics. Methods: Rats were given drinking water containing 1 mg/ml penicillin and 2 mg/ml streptomycin from 5 days before the administration
of CPT-11 (60 mg/kg i.v.) and throughout the experiment. CPT-11, SN-38 glucuronide and SN-38 concentrations in the blood,
intestinal tissues and intestinal luminal contents were determined by HPLC. Results: Antibiotics had little or no effect on the pharmacokinetics of CPT-11, SN-38 glucuronide or SN-38 in the blood, or in the
tissues or contents of the small intestine, which has less β-glucuronidase activity in its luminal contents. In contrast,
antibiotics markedly reduced the AUC1–24 h of SN-38 (by about 85%) in the large intestine tissue without changing that of CPT-11, and this was accompanied by a complete
inhibition of the deconjugation of SN-38 glucuronide in the luminal contents. Conclusions: These results suggest that SN-38, which results from the hydrolysis of SN-38 glucuronide by β-glucuronidase in the intestinal
microflora, contributes considerably to the distribution of SN-38 in the large intestine tissue, and that inhibition of the
β-glucuronidase activity by antibiotics results in decreased accumulation of SN-38 in the large intestine.
Received: 8 August 1997 / Accepted: 16 January 1998 相似文献
992.
Toshiro Hara M.D. Yumi Mizuno M.D. Yoshiko Ikuno M.D. Jun Okamura M.D. Mari Nagata M.D. Eiichi Ishii M.D. Shinichi Yamada M.D. Hideko Tasaka M.D. Kohji Ueda M.D. 《Pediatrics international》1990,32(5):515-518
Thirty-six (17.8%) of 202 children with acute lymphoblastic leukemia (ALL) and 2 (3.7%) of 54 children with acute nonlymphoblastic leukemia (ANLL) had a platelet count over 150 times 109 /1 at diagnosis. Children with ALL and a platelet count over 150 times 109 /1 were analysed in detail. The ALL patients without thrombocytopenia tended to be male predominant and had less frequent bleeding manifestations (p < 0.01).These patients without thrombocytopenia had also significantly less marked leukocytosis (p < 0.01), less severe anemia (p < 0.05) and lower percentages of bone marrow blasts (p < 0.05) than those with thrombocytopenia. In addition, ALL patients without thrombocytopenia had a significantly higher probability of continuous complete remission than those with thrombocytopenia (p < 0.01). 相似文献
993.
Eiichi Ishii M.D. Yasufumi Okabe M.D. Kanji Sakamoto M.D. Kohji Ueda M.D. Kanehiro Hasuo M.D. 《Pediatrics international》1986,28(1):94-97
We treated a child with acute lymphoblastic leukemia who developed central nervous system leukemia and obesity due to Cushing syndrome. The infiltration of leukemic cells was gradually ameliorated with intrathecal nethotrexate therapy. At the same time, clinical symptoms of Cushing syndrome have almost normalized. The relation between central nervous system leukemia and Cushing syndrome is discussed. 相似文献
994.
Konishi E Nakashima Y Smyrk TC Masuda S 《Archives of pathology & laboratory medicine》2003,127(6):745-747
A golden yellow polyp was detected in the gallbladder of a 64-year-old man who presented with epigastric pain. The lesion was composed of clear polygonal cells arranged in a trabecular and glandular pattern. The tumor invaded through the wall into the perimuscular subserosal layer. Immunohistochemical stains showed that neoplastic cells were positive for chromogranin A, synaptophysin, somatostatin, gastrin, and pancreatic polypeptide and negative for glucagon, serotonin, insulin, S100 protein, and inhibin. This tumor resembles the recently described clear cell endocrine tumors of the gallbladder and pancreas that are associated with von Hippel-Lindau disease. Our patient, however, had neither personal nor family history indicative of von Hippel-Lindau disease. Furthermore, published accounts of clear cell endocrine tumors in von Hippel-Lindau disease describe immunoreactivity for inhibin; the current case was negative for the disease. There may be a subtype of clear cell carcinoid tumor not associated with von Hippel-Lindau disease, which is characterized by its lack of immunoreactivity against inhibin. 相似文献
995.
Neurofibrillary tangles (NFT) are present in the subthalamic nucleus (STN) of progressive supranuclear palsy and corticobasal degeneration, two sporadic tauopathies with preferential accumulation of tau with four repeats in the microtubule binding domain (4R tau). Since recent evidence suggests that argyrophilic grain disease (AGD) is also a 4R tauopathy, we hypothesized that the STN may also be affected in AGD. Tau immunostaining was used to evaluate NFT in the STN in 18 cases of AGD compared with 18 non-AGD cases matched for age, sex and Braak stage. AGD cases had significantly more NFT in the STN than non-AGD cases (P=0.008) with no relationship between NFT score and Braak stage. Surprisingly, NFT were also found in the STN of some non-AGD cases, notably in cases with advanced Braak stage (i.e. Alzheimer's disease). When AGD and non-AGD were considered as a whole there was a correlation between neurofibrillary degeneration in the STN and Braak stage. This study demonstrates that neurofibrillary degeneration is frequent in the STN in AGD, but also detected in non-AGD cases with advanced Braak stage. 相似文献
996.
Kenji Kuba Eiichiro Tanaka Eiichi Kumamoto Shoichi Minota 《Pflügers Archiv : European journal of physiology》1989,414(2):105-112
Nicotinic acetylcholine-receptor ion channels (AChR channels) were studied in bullfrog sympathetic ganglion cells cultured for 1 day to 3 weeks, using a patch clamp technique. Microsuperfusion of ACh (2–10 M) to the ganglion cell under the whole cell clamp produced an inward current at membrane potentials negative to –60 mV, which had a fast onset and decay. This rapid ACh-induced current was accompanied by a large current fluctuation, decreased and increased in amplitude by membrane depolarization and hyperpolarization, respectively, and blocked by d-tubocurarine. Thus, this current must be induced by the nicotinic action of ACh, but not by a muscarinic effect to activate a slow cation-selective current. At depolarized levels more than –50 mV, Ach induced an additional inward current which was slow in time course, accompanied by no or decreased current fluctuation and increased in amplitude by membrane depolarization. Accordingly, this slow ACh-induced current could result from the suppression of a voltage-dependent K+ current (M-current: Brown and Adams 1980) by the muscarinic action of ACh. Fluctuation analysis of the rapid ACh-induced current at potentials negative to –50 mV revealed the elementary conductance of 14 pS and a power spectral density distribution of the double Lorentzian function which yielded the time constants of 5.4 and 62.5 ms at –60 to –80 mV. The variance of either component was independent of the mean current.Under both the cell-attached and outside-out modes, ACh (1–10 M: applied by microsuperfusion or bath application for the latter mode) caused single channel currents which reversed at a membrane potential close to 0 mV and had a conductance of 18–28 pS. In some patches, single channel currents of a smaller conductance (12 pS) were also observed in the presence of ACh. The open time distribution of the main AChR channel population followed a single or double exponential function depending on patches. The time constant of the single exponential distribution and that of the fast component of the double exponential distribution were similar and approximately 0.9 ms, while that of the slow component of the latter was 6.4 ms. Furthermore, the magnitude of each component in double exponential distributions varied largely among patches. These results suggest that there are at least two or three types of AChR channels in cultured bullfrog sympathetic ganglion cells: fast and slow AChR channels of 18–28 pS and possibly a fast AChR channel of smaller conductance of 12 pS. 相似文献
997.
The effects of zinc on interleukin-2(IL-2)-dependent T cell responses of lymphocytes from immunodepressed aged mice and from young adult animals were studied. Concentrations of zinc which have been shown to restore antibody formation in cells from aged mice and to increase the production of Il-1 and Il-4 inhibited the production of Il-2. Cells from both young adults and aged mice were inhibited similarly. Zinc also impaired the ability of aged T cells to proliferate in response to concanavalin A and exogenous Il-2, but enhanced the proliferation of similarly activated splenic cultures containing both T and B cells. Cultures of isolated B lymphocytes produced antibody to sheep red blood cells if the cells were provided with supplemental zinc and Il-1. In contrast, recombinant Il-2 with or without zinc did not activate antibody formation. The results support the premise that the restorative effects of zinc are independent of Il-2 and that Il-2 is not a necessary mediator for antibody production in the aged. 相似文献
998.
999.
Kimura N Togo A Sugimoto T Nata K Okamoto H Nagatsu I Nagura H 《Endocrine pathology》1996,7(2):131-136
Pheochromocytoma is a catecholamine (CA)-producing tumor that is classified into two types: the norepinephrine (NE) and the
mixed NE and epinephrine type (E-type) from plasma CA levels. Phenylethanolamine N-methyltransferase (PNMT) is the terminal
enzyme in CA synthesis; it catalyzes the synthesis of E from NE. It is not known whether the absence of immunoreactive PNMT
is paralleled by a lack of PNMT mRNA. The mRNA of tyrosine hydroxylase (TH) and PNMT in seven pheochromocytomas, five NE-type
and two E-type tumors, were examined by Northern blot analysis andin situ hybridization (ISH) technique. TH mRNA was detected in all tumors but PNMT mRNA was limited only to the E-type tumors. In
addition to our previous immunohistochemical study of 70 pheochromocytomas and paragangliomas in which all pheochromocytomas
had cells immunoreactive to TH, but PNMT was expressed only in E-type, we concluded that NE-type pheochromocytoma lacks PNMT
both at the mRNA and protein levels, resulting in an inability to produce E. The essential difference between NE-type and
E-type pheochromocytoma is that the NE-type lacks PNMT. 相似文献
1000.
Miura S Tanaka E Mori A Toya M Takahashi K Nakahara K Ohmichi M Kurachi H 《Maturitas》2003,45(4):293-298
Objectives: Aortic stiffness, determined by the pulse wave velocity (PWV), is an independent marker of cardiovascular risk. PWV is mainly influenced by age-associated alterations of arterial wall structure and blood pressure (BP). To determine the impact of hormone replacement therapy (HRT) on arterial compliance in normotensive, postmenopausal women, we examined the effects of HRT on PWV. Methods: Fifty-six postmenopausal women aged 50–70 years were recruited into the present retrospective study from the patients visiting our menopause clinic. Twenty-seven women who were prescribed HRT (14 on estrogen alone and 13 on estrogen plus progestogen) for several months to 6 years and an age-matched group of 29 women not on HRT were studied (Study 1). Nine postmenopausal women were also studied before and at 4 weeks of the treatment of estrogen replacement therapy (ERT) (Study 2). Brachial to ankle PWV (baPWV), which is correlated with aortic PWV, was determined using an automatic device, BP-203PRE. Results: In Study 1, PWV was significantly correlated with age in both groups (controls: r=0.392, P=0.035; HRT group: r=0.471, P=0.013), and HRT significantly lowered the PWV value at all ages examined (Mean±S.D. of baPWV in controls: 1382.2±114.1; HRT: 1245.3±124.8, P=0.0001). In Study 2, baPWV decreased significantly after ERT (P<0.05), without a significant change in systolic BP (P=0.851). Conclusions: Estrogen appears to improve arterial compliance independently of BP within 4 weeks. 相似文献