全文获取类型
收费全文 | 1289篇 |
免费 | 30篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 72篇 |
儿科学 | 66篇 |
妇产科学 | 55篇 |
基础医学 | 151篇 |
口腔科学 | 16篇 |
临床医学 | 68篇 |
内科学 | 303篇 |
皮肤病学 | 18篇 |
神经病学 | 150篇 |
特种医学 | 10篇 |
外科学 | 72篇 |
综合类 | 6篇 |
预防医学 | 77篇 |
眼科学 | 46篇 |
药学 | 151篇 |
中国医学 | 3篇 |
肿瘤学 | 62篇 |
出版年
2023年 | 3篇 |
2022年 | 7篇 |
2021年 | 21篇 |
2020年 | 6篇 |
2019年 | 13篇 |
2018年 | 12篇 |
2017年 | 9篇 |
2016年 | 18篇 |
2015年 | 27篇 |
2014年 | 21篇 |
2013年 | 39篇 |
2012年 | 73篇 |
2011年 | 87篇 |
2010年 | 33篇 |
2009年 | 35篇 |
2008年 | 86篇 |
2007年 | 114篇 |
2006年 | 141篇 |
2005年 | 127篇 |
2004年 | 110篇 |
2003年 | 98篇 |
2002年 | 124篇 |
2001年 | 8篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 8篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 4篇 |
排序方式: 共有1326条查询结果,搜索用时 15 毫秒
101.
Little is known about the mechanisms of apoptosis triggered in normal cells of the haemopoietic system by the aminothiol WR-2721 (Amifostine), chemotherapeutic drugs, and ionizing radiation; thus, the present study was undertaken to evaluate the effects of WR-2721, cyclophosphamide (CP), cisplatin (CDDP), and 60Co gamma rays on induction of apoptotic DNA degradation in bone marrow cells. Adult male Swiss mice were treated with WR-2721 (400 mg/kg b.wt.), CP (200 mg/kg b.wt.), and CDDP (10 mg/kg b.wt.), and exposed to 6 Gy 60Co gamma rays. Alterations in the number of apoptotic cells with fractional DNA content and also the cell cycle position of the non-apoptotic cells were determined in the bone marrow at 7 and 24 hours after treatment of mice with these agents, using flow cytometric assay of the controlled extraction of low-MW DNA from apoptotic cells. The chemotherapeutic drugs CP and CDDP and 60Co gamma rays triggered apoptosis and affected the cell cycle position of the non-apoptotic cells in the mouse bone marrow. The pretreatment of mice with WR-2721 resulted in the modulatory action of the aminothiol on induction of apoptotic cell death and changes in the cell cycle distribution of the non-apoptotic cells caused by the DNA-damaging agents. The patterns of changes in the frequency of apoptotic cells and the cell cycle position of the non-apoptotic cells, observed in the bone marrow, were dependent on the agent(s) applied and the time interval after application of the drug(s) and exposure of mice to gamma rays. Understanding of the mechanisms responsible for triggering of apoptotic cell death and disturbing of the cell cycle by the DNA-damaging agents, and modulation of the apoptotic and cell cycle pathways by the aminothiol WR-2721, can lead to more effective therapy and chemo- and radio-protection of normal cells. 相似文献
102.
Adaptation is a central concept of modern evolutionary biology, but remains a difficult one nevertheless. Definitions of adaptation are often confounded with definitions of natural selection, rendering them somewhat circular and difficult to operationalize. Williams introduced a definition that avoids such tautology and a strategy for testing adaptive claims against chance as an alternative explanation for design complexity. Gould and Lewontin ([1979]: Proc R Soc Lond B Biol Sci 205:581-598) challenged this strategy for pitting adaptation against a straw alternative, and argued that constraint is often the cause of design complexity. The field of Darwinian medicine has underscored the fact that adaptation can also be difficult to discriminate from pathology, which can also produce design complexity. We suggest that an updated version of Williams' strategy is to consider any claim of adaptation against constraint and pathology as alternatives. We use an example drawn from the intersection of human reproductive ecology and developmental biology to illustrate how this updated strategy can be applied. Where we can generate distinct predictions for the three alternative hypotheses, constraint, pathology, and adaptation, we have a better situation in which to evaluate adaptive claims with a real possibility of falsification. We view this strategy as an improvement over Williams' original suggestion, but not as a definitive strategy. Further advances, however, will likely also be based on a sound understanding of the concept of adaptation and the identification of the strongest competing alternatives to it. 相似文献
103.
Rademacher PM Woods CM Huang Q Szklarz GD Nelson SD 《Chemical research in toxicology》2012,25(4):895-903
The uricosuric diuretic agent tienilic acid (TA) is a thiophene-containing compound that is metabolized by P450 2C9 to 5-OH-TA. A reactive metabolite of TA also forms a covalent adduct to P450 2C9 that inactivates the enzyme and initiates immune-mediated hepatic injury in humans, purportedly through a thiophene-S-oxide intermediate. The 3-thenoyl regioisomer of TA, tienilic acid isomer (TAI), is chemically very similar and is reported to be oxidized by P450 2C9 to a thiophene-S-oxide, yet it is not a mechanism-based inactivator (MBI) of P450 2C9 and is reported to be an intrinsic hepatotoxin in rats. The goal of the work presented in this article was to identify the reactive metabolites of TA and TAI by the characterization of products derived from P450 2C9-mediated oxidation. In addition, in silico approaches were used to better understand both the mechanisms of oxidation of TA and TAI and/or the structural rearrangements of oxidized thiophene compounds. Incubation of TA with P450 2C9 and NADPH yielded the well-characterized 5-OH-TA metabolite as the major product. However, contrary to previous reports, it was found that TAI was oxidized to two different types of reactive intermediates that ultimately lead to two types of products, a pair of hydroxythiophene/thiolactone tautomers and an S-oxide dimer. Both TA and TAI incorporated 1?O from 1?O? into their respective hydroxythiophene/thiolactone metabolites indicating that these products are derived from an arene oxide pathway. Intrinsic reaction coordinate calculations of the rearrangement reactions of the model compound 2-acetylthiophene-S-oxide showed that a 1,5-oxygen migration mechanism is energetically unfavorable and does not yield the 5-OH product but instead yields a six-membered oxathiine ring. Therefore, arene oxide formation and subsequent NIH-shift rearrangement remains the favored mechanism for formation of 5-OH-TA. This also implicates the arene oxide as the initiating factor in TA induced liver injury via covalent modification of P450 2C9. Finally, in silico modeling of P450 2C9 active site ligand interactions with TA using the catalytically active iron-oxo species revealed significant differences in the orientations of TA and TAI in the active site, which correlated well with experimental results showing that TA was oxidized only to a ring carbon hydroxylated product, whereas TAI formed both ring carbon hydroxylated products and an S-oxide. 相似文献
104.
Malaeb SN Hovanesian V Sarasin MD Hartmann SM Sadowska GB Stonestreet BS 《Journal of neuroscience research》2009,87(1):179-189
We examined the effects of single and multiple maternal glucocorticoid courses on apoptosis in the cerebral cortices of ovine fetuses (CC). Ewes received single dexamethasone or placebo courses at 104-106 or 133-135 days or multiple courses between 76-78 and 104-106 days gestation. In the single-course groups, ewes received four 6 mg dexamethasone or placebo injections every 12 hr for 48 hr. Multiple-course groups received the same treatment once per week for 5 weeks. Neuronal and nonneuronal apoptotic cell numbers per square millimeter were determined with TUNEL and NeuN staining and with caspase-3 enzyme activity on CC tissues harvested at 106-108 (70%) or 135-137 (90%) days of gestation. Apoptotic cell numbers and caspase-3 activity were 50% lower (P < 0.02) after single placebo courses at 90% than 70% gestation; 90% of apoptotic cells were (P < 0.01) nonneuronal at both ages. Nonneuronal apoptotic cells and caspase-3 activity were 40% and 20% lower (P < 0.02) after single dexamethasone than placebo courses at 70%, but not 90%, gestation. Caspase-3 activity was 20% lower (P < 0.01) after multiple dexamethasone than placebo courses, but apoptotic cell number did not differ. We conclude that nonneuronal apoptosis represents the major form of apoptosis in the CC at both 70% and 90% of gestation. Apoptosis in nonneuronal cells decreases with maturity and after a single course of dexamethasone at 70%, but not at 90%, gestation and not after multiple courses at 70% gestation. We speculate that a single course of glucocorticoids exerts maturational changes on the rate of apoptosis in the cerebral cortex of preterm ovine fetuses. 相似文献
105.
106.
BACKGROUND: Sarcoidosis (SA) is a multisystem granulomatous disorder of unknown etiology. It seems likely that in genetically different predisposed hosts, the same antigen(s) may cause the development of sarcoid Th1 response. The interaction of the T-cell receptor with the human leukocyte antigen-DQA1*03011 peptide-complex can affect T lymphocytes activation in a dose-response manner. OBJECTIVES/METHODS: To test occurrence of DQA1*03011 allele in SA, we compared the distribution of DQA1 alleles in 32 SA patients, 37 TB patients and in 58 healthy volunteers, using a PCR-SSP "high-resolution" method. RESULTS: Our results revealed that after Bonferroni correction DQA1*03011 were less common in SA patients than in the controls (OR 0.16, 95%CI 0.03-0.75). In TB, DQA1*0303 were significantly more frequent and DQA1*0505 less present as compared to the controls (OR 11.03, 95% CI 1.20-95.80, OR 0.29, 95% CI 0.01-0.88). Comparing DQA1 alleles in both patient groups, DQA1*0501, DQA1*0505 alleles were more common and DQA1*03011, DQA1*0302, DQA1*0303 were less common after Bonferroni correction in SA than in TB. CONCLUSION: We revealed that DQA1*03011 allele was less common in SA than in the controls and TB. It seems possible that a low frequency of DQA1*03011 occurrence may be also involved in the etiopathogenesis of SA. 相似文献
107.
A 72-year-old male diagnosed with heart failure and dyspnea was found to have a lesion in his right atrium. Histological examination of the tumor revealed it to be a malignant fibrous histiocytoma. The patient's management and subsequent follow-up are presented. 相似文献
108.
109.
110.
Nowak G Clifton GL Bakajsova D 《The Journal of pharmacology and experimental therapeutics》2008,324(3):1155-1162
We previously reported that mitochondrial function, intracellular ATP levels, and complex I activity are decreased in renal proximal tubular cells (RPTC) after oxidant (tert-butyl hydroperoxide; TBHP)-induced injury. This study examined the hypothesis that succinate supplementation decreases mitochondrial dysfunction, ameliorates energy deficits, and increases viability in TBHP-injured RPTC. Basal and uncoupled respirations in injured RPTC decreased 33 and 35%, respectively, but remained unchanged in injured RPTC supplemented with 10 mM succinate (electron donor to respiratory complex II). State 3 respiration supported by electron donors to complex I decreased 40% in injured RPTC but improved significantly by succinate supplements. The activity of mitochondrial complex I in TBHP-injured RPTC decreased 48%, whereas complex II activity remained unchanged. Succinate supplementation prevented decreases in complex I activity. ATP levels decreased 43% in injured RPTC but were maintained in injured cells supplemented with succinate. Lipid peroxidation increased 19-fold in injured RPTC but only 9-fold in injured cells supplemented with succinate. Exposure of primary cultures of RPTC to TBHP produced 24% cell injury and lysis but no apoptosis. In contrast, no cell lysis was found in RPTC supplemented with succinate. We conclude that mitochondrial dysfunction and energy deficits in oxidant-injured RPTC are ameliorated by succinate, and we propose that succinate supplementation may prove therapeutically valuable. Succinate 1) uses an alternate pathway of mitochondrial energy metabolism, 2) improves activity of complex I and oxidation of substrates through complex I, and 3) decreases oxidative stress and cell lysis in oxidant-injured RPTC. 相似文献