全文获取类型
收费全文 | 10532篇 |
免费 | 527篇 |
国内免费 | 55篇 |
专业分类
耳鼻咽喉 | 188篇 |
儿科学 | 118篇 |
妇产科学 | 206篇 |
基础医学 | 1453篇 |
口腔科学 | 248篇 |
临床医学 | 711篇 |
内科学 | 2653篇 |
皮肤病学 | 147篇 |
神经病学 | 897篇 |
特种医学 | 442篇 |
外国民族医学 | 1篇 |
外科学 | 1744篇 |
综合类 | 70篇 |
一般理论 | 1篇 |
预防医学 | 358篇 |
眼科学 | 113篇 |
药学 | 744篇 |
中国医学 | 35篇 |
肿瘤学 | 985篇 |
出版年
2023年 | 51篇 |
2022年 | 102篇 |
2021年 | 144篇 |
2020年 | 78篇 |
2019年 | 102篇 |
2018年 | 137篇 |
2017年 | 102篇 |
2016年 | 97篇 |
2015年 | 116篇 |
2014年 | 197篇 |
2013年 | 201篇 |
2012年 | 411篇 |
2011年 | 468篇 |
2010年 | 278篇 |
2009年 | 278篇 |
2008年 | 443篇 |
2007年 | 477篇 |
2006年 | 479篇 |
2005年 | 454篇 |
2004年 | 498篇 |
2003年 | 434篇 |
2002年 | 490篇 |
2001年 | 442篇 |
2000年 | 492篇 |
1999年 | 411篇 |
1998年 | 136篇 |
1997年 | 104篇 |
1996年 | 107篇 |
1995年 | 83篇 |
1994年 | 73篇 |
1993年 | 84篇 |
1992年 | 321篇 |
1991年 | 277篇 |
1990年 | 294篇 |
1989年 | 271篇 |
1988年 | 241篇 |
1987年 | 229篇 |
1986年 | 197篇 |
1985年 | 193篇 |
1984年 | 140篇 |
1983年 | 110篇 |
1979年 | 76篇 |
1978年 | 61篇 |
1977年 | 74篇 |
1975年 | 54篇 |
1974年 | 59篇 |
1973年 | 48篇 |
1972年 | 57篇 |
1969年 | 51篇 |
1968年 | 61篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
81.
A pedigree analysis with minimised ascertainment bias shows anticipation in Met30-transthyretin related familial amyloid polyneuropathy. 总被引:3,自引:0,他引:3 下载免费PDF全文
In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the affected parent in 68 parent-child pairs (including data on assumed age at onset and on asymptomatic obligate heterozygotes and parents at obligate 50% risk) in 15 families. Excluding the parent-child pairs involving the proband and "bilineal pairs", onset occurred earlier in the child than in the transmitting parent in 60 out of 68 "unilineal pairs". After correction for ascertainment bias resulting from incomplete penetrance and reduced biological fitness in early onset patients, the number of anticipation pairs (60 pairs) was still significantly larger than that of non-anticipation pairs (29.7 pairs) (p < 0.05). When the children were sons, the difference in age at onset was significantly greater in the mother-son pairs than in the father-son pairs (p = 0.023). Although not all ascertainment biases could be eliminated, these data show strong evidence that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon. 相似文献
82.
K. Ando N. Umetani T. Kurosawa S. Takeda Y. Katoh F. Marumo 《Journal of molecular medicine (Berlin, Germany)》1988,66(17):768-772
Summary A highly sensitive radioimmunoassay to measure atrial natriuretic peptide (ANP) concentration in urine has been established, and its clinical usefulness is presented. ANP in urine was stable at 4° C for several days and was easily measured by our radioimmunoassay. The average ANP excretion in 65 healthy persons was 25.0±1.4 ng/day (mean ± SEM) and the fractional excretion of ANP was 0.7±0.05%. In 14 patients with congestive heart failure, the average ANP excretion was 119.2±29.4 ng/day, which decreased to 53.3±11.0 after successful treatment.Abbreviations ANP
atrial natriuretic peptide
- hANP
human atrial natriuretic peptide
- RIA
radioimmunoasay
- NSB
non specific bound
- FEANP
the fractional excretion of atrial natriuretic peptide
- FENa
the fractional excretion of sodium
- SIADH
the syngrome of inappropriate secretion of antidiuretic hormone 相似文献
83.
Park JW Taube C Swasey C Kodama T Joetham A Balhorn A Takeda K Miyahara N Allen CB Dakhama A Kim SH Dinarello CA Gelfand EW 《American journal of respiratory cell and molecular biology》2004,30(6):830-836
The role of an interleukin (IL)-1 receptor antagonist (IL-1Ra) on the development of airway hyperresponsiveness (AHR) and airway inflammation following acute O(3) exposure in mice was investigated. Exposure of C57/BL6 mice to O(3) at a concentration of 2.0 ppm or filtered air for 3 h resulted in increases in airway responsiveness to inhaled methacholine (MCh) 8 and 16 h after the exposure, and an increase in neutrophils in the bronchoalveolar lavage (BAL) fluid. IL-1beta expression, assessed by gene microarray, was increased 2-fold 4 h after O(3) exposure, and returned to baseline levels by 24 h. Levels of IL-1beta in lung homogenates were also increased 8 h after O(3) exposure. Administration of (human) IL-1Ra before and after O(3) exposure prevented development of AHR and decreased BAL fluid neutrophilia. Increases in chemokine levels in lung homogenates, tumor necrosis factor-alpha, MIP-2, and keratinocyte chemoattractant following O(3) exposure were prevented by IL-1Ra. Inhalation of dexamethasone, an inhibitor of IL-1 production, blocked the development of AHR, BAL fluid neutrophilia, and decreased levels of IL-1 following O(3) exposure. In summary, acute exposure to O(3) induces AHR, neutrophilic inflammation, epithelial damage, and IL-1. An IL-1Ra effectively prevents the development of altered airway function, inflammation, and structural damage. 相似文献
84.
K Hashizume K Ichikawa A Sakurai S Suzuki T Takeda M Kobayashi T Miyamoto M Arai T Nagasawa 《The New England journal of medicine》1991,324(14):947-953
BACKGROUND. Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole. METHODS AND RESULTS. The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/- 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole. CONCLUSIONS. The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism. 相似文献
85.
Masaru Enomoto Akihiro Tamori Madoka Toyama Kohmoto Takehiro Hayashi Hisato Jomura Daiki Habu Hiroki Sakaguchi Tadashi Takeda Norifumi Kawada Shuichi Seki Susumu Shiomi Noritoshi Koh Shuhei Nishiguchi 《Journal of interferon & cytokine research》2007,27(3):201-207
Sequential treatment with lamivudine and interferon (IFN) has induced sustained biochemical and virologic responses in the majority of patients with chronic hepatitis B in France. However, the efficacy of sequential treatment in patients with chronic hepatitis B virus (HBV) genotype C infection has not been evaluated. Twenty-four HBe antigen-positive patients were treated with 100 mg lamivudine alone for 16-32 weeks, then with both 6 MU IFN-beta and lamivudine for 4 weeks, and lastly with IFN-beta alone for 20 weeks. Sustained response was achieved in 7 (29%) patients 24 weeks after the end of therapy. No lamivudine-resistant variants emerged in any patient. Hepatitis flare occurred in 3 patients after the withdrawal of lamivudine, but none had decompensation. The patients with sustained response were significantly younger at baseline (p = 0.033) and had a significantly lower HBV DNA level at the start of IFN (p = 0.020) than those without sustained response. In conclusion, the rate of response to sequential therapy with lamivudine and IFN in HBe antigen-positive patients with HBV genotype C infection was lower than the rate reported previously. Patients who were young or who had a favorable virologic response to lamivudine were more likely to have a sustained response. 相似文献
86.
The effects of omega-conotoxin (omega-CgTX) on voltage-sensitive Ca currents (ICa) were studied in cultured bovine adrenal chromaffin cells. A maximal block of ICa of 40-50% was obtained with omega-CgTX in the microM range, and was independent of the holding potential. The onset of block was both concentration- and time-dependent. In bovine chromaffin cells, Ca channels, both sensitive and insensitive to omega-CgTX, appear to be present. 相似文献
87.
An interleukin-3-dependent progenitor clone LyD9 and its interleukin-4-dependent derivative clone K-4 were shown to differentiate into myeloid cells as well as B lymphocytes by coculture with bone marrow stroma cells. The K-4 clone is an intermediate between myeloid/lymphoid cells and the LyD9 clone that requires interleukin-4 for differentiation into B lymphocytes and myeloid cells. Granulocyte-macrophage colony stimulating factor-dependent derivatives (LS-1 and K-GM) were also established from induced LyD9 cells. LS-1 and K-GM were myeloid-committed cells. 相似文献
88.
T. Yambe S. Nanka S. Naganuma S. Kobayashi S. Nitta T. Fukuju N. Uchida K. Tabayashi A. Tanaka K. Abe H. Takayasu M. Yoshizawa H. Takeda 《Journal of artificial organs》2002,5(1):1-5
Artificial circulation has been analyzed by decomposing it into parts. However, the sum of the decomposed parts is not equal
to the whole system, especially in nonlinear dynamic systems such as biological systems. To evaluate prosthetic circulation
as an entity, not as decomposed parts, nonlinear mathematical analytic techniques, including fractal dimension analyzing theory,
were used. Two pneumatically actuated ventricular assist devices were implanted as biventricular bypasses (BVB) in chronic
animal experiments using four healthy adult goats. For comparison between natural and prosthetic circulation in the same experimental
animals, the BVB-type complete prosthetic circulation model with ventricular fibrillation was adopted. All hemodynamic parameters
with natural and prosthetic circulation were recorded under awake conditions and calculated by a personal computer system.
By the use of nonlinear mathematical techniques, time-series data of the hemodynamics were embedded into the phase space,
and correlation dimension analysis was performed to evaluate the reconstructed attractor. Our results suggest that the correlation
dimension of the arterial blood pressure does not linearly increase according to the increase of the embedding dimension,
even during artificial circulation, suggesting those are the fractal time series data. Dimensional analysis of the hemodynamics
revealed that lower dimensional fractal dynamics were observed during prosthetic circulation. Fractal time series data are
suggested to have robustness and error resistance. Thus, our results suggest that the circulatory regulatory system with the
artificial heart may have these desirable characteristics.
Accepted: July 14, 1995 相似文献
89.
ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats 总被引:28,自引:1,他引:28
Nishitoh H Matsuzawa A Tobiume K Saegusa K Takeda K Inoue K Hori S Kakizuka A Ichijo H 《Genes & development》2002,16(11):1345-1355
Expansion of CAG trinucleotide repeats that encode polyglutamine is the underlying cause of at least nine inherited human neurodegenerative disorders, including Huntington's disease and spinocerebellar ataxias. PolyQ fragments accumulate as aggregates in the cytoplasm and/or in the nucleus, and induce neuronal cell death. However, the molecular mechanism of polyQ-induced cell death is controversial. Here, we show the following: (1) polyQ with pathogenic repeat length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, proteasome inhibitor-, and ER stress-induced JNK activation and cell death. These findings suggest that ASK1 is a key element in ER stress-induced cell death that plays an important role in the neuropathological alterations in polyQ diseases. 相似文献
90.
Nakashima I Kato M Akhand AA Suzuki H Takeda K Hossain K Kawamoto Y 《Antioxidants & redox signaling》2002,4(3):517-531
The signaling for activation of protein tyrosine kinases (PTKs) is usually started by binding of ligands to cell-surface receptors. However, recent evidence suggests the presence of ligand binding-independent signaling pathways that are mediated by oxidative stress. Oxidation and reduction of protein cysteine sulfhydryl (SH) groups may work as a molecular switch to start or to stop the signaling. It is known that oxidation of cysteine SH groups on protein tyrosine phosphatases switches off the action of protein tyrosine phosphatases. This event may not, however, signal for initial autophosphorylation of previously unphosphorylated PTKs, whereas it certainly prevents dephosphorylation of once-phosphorylated PTKs. We have suggested new mechanisms for oxidative stress-mediated PTK activation. First, cell-surface glycosylphosphatidylinositol-anchoring proteins and a phosphoglycolipid/cholesterol-enriched membrane microdomain termed a "raft" can be the direct targets of oxidative stress for inducing their clustering through an S-S-bonded or S-X-S-bonded crosslinking of cell-surface proteins and subsequent activation of raft-associating Src family PTKs. Second, intracellular specific cysteine SH groups on PTK proteins can be another target of oxidative stress for inducing a conformational change necessary for initial activation of PTKs. A possible relationship between cell-surface and intracellular events is that the former frequently induces superoxide production as the second messenger for the latter. 相似文献