全文获取类型
收费全文 | 14762篇 |
免费 | 1076篇 |
国内免费 | 65篇 |
专业分类
耳鼻咽喉 | 203篇 |
儿科学 | 247篇 |
妇产科学 | 201篇 |
基础医学 | 2210篇 |
口腔科学 | 158篇 |
临床医学 | 1522篇 |
内科学 | 3601篇 |
皮肤病学 | 388篇 |
神经病学 | 1414篇 |
特种医学 | 645篇 |
外国民族医学 | 10篇 |
外科学 | 2300篇 |
综合类 | 40篇 |
一般理论 | 5篇 |
预防医学 | 678篇 |
眼科学 | 198篇 |
药学 | 943篇 |
中国医学 | 14篇 |
肿瘤学 | 1126篇 |
出版年
2024年 | 18篇 |
2023年 | 161篇 |
2022年 | 279篇 |
2021年 | 646篇 |
2020年 | 345篇 |
2019年 | 537篇 |
2018年 | 646篇 |
2017年 | 414篇 |
2016年 | 474篇 |
2015年 | 544篇 |
2014年 | 724篇 |
2013年 | 863篇 |
2012年 | 1300篇 |
2011年 | 1280篇 |
2010年 | 693篇 |
2009年 | 628篇 |
2008年 | 961篇 |
2007年 | 932篇 |
2006年 | 798篇 |
2005年 | 743篇 |
2004年 | 635篇 |
2003年 | 540篇 |
2002年 | 473篇 |
2001年 | 104篇 |
2000年 | 103篇 |
1999年 | 90篇 |
1998年 | 87篇 |
1997年 | 59篇 |
1996年 | 59篇 |
1995年 | 56篇 |
1994年 | 45篇 |
1993年 | 39篇 |
1992年 | 56篇 |
1991年 | 63篇 |
1990年 | 55篇 |
1989年 | 48篇 |
1988年 | 35篇 |
1987年 | 36篇 |
1986年 | 33篇 |
1985年 | 20篇 |
1984年 | 26篇 |
1983年 | 31篇 |
1982年 | 34篇 |
1981年 | 14篇 |
1980年 | 15篇 |
1979年 | 18篇 |
1978年 | 16篇 |
1977年 | 13篇 |
1974年 | 14篇 |
1972年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
91.
Thomas Stroheker Nicolas Cabaton Raymond Berges Valérie Lamothe Jean-Claude Lhuguenot Marie Christine Chagnon 《Food and chemical toxicology》2003,41(8):1175-1183
We evaluated the effects of three rodent diets differing in soybean meal content on the response of the seminal vesicles, prostate and bulbocavernosus/levator ani (BC/LA) muscle to androgens and anti-androgenic compounds in the Hershberger assay. The diets tested were (1) L5, a semi-synthetic phytoestrogen-free diet, (2) DO4, 8.5% (w/w) vegetable protein and (3) DO3, 22.5% (w/w) vegetable protein. We determined the effects of dietary soy isoflavones after ten days of exposure and in animals fed L5 and DO3 diets throughout their lifetime (including the period of treatment with androgenic or anti-androgenic compounds). After ten days of exposure, we observed no effect of diet on the accessory sex organs of male Wistar rats. In contrast, diet affected the androgenic response to testosterone propionate in seminal vesicles and prostate. Seminal vesicles were the most sensitive organs. Vinclozolin caused a dose-dependent decrease in the relative weights of seminal vesicles, prostate and BC/LA regardless of diet. As vegetable proteins may contain high proportions of genistein and daidzein, two well-known oestrogenic endocrine disrupters that may alter the results of reproductive studies, we recommend the use of a standardised open-formula diet without soy isoflavones, such as L5, if the Hershberger assay is to be performed. 相似文献
92.
BACKGROUND AND PURPOSE: There is still confusion in the choice of the molecular assays to predict the radiation response of human cells. The case of tumours appears to be particularly complex, may be because of their instability and heterogeneity. The aim of this study was to investigate quantitatively the relationships between DNA double-strand breaks (DSB) repair, chromatin relaxation and cellular radiosensitivity. Nineteen human tumour cell lines, representing a large spectrum of radiation responses and tissues, were examined. MATERIALS AND METHODS: Intrinsic radiosensitivity was quantified with surviving fraction at 2 Gy (SF2) as an endpoint. Standard and modified pulsed-field gel electrophoresis techniques were employed to assess DSB repair rate and chromatin relaxation. A cell-free assay was chosen to estimate DSB repair activity, independently of chromatin impairment. RESULTS AND CONCLUSIONS: Surviving fraction at 2 Gy (SF2) decreases linearly with the amount of unrepaired DSB and the extent of chromatin relaxation: one additional unrepaired DSB per cell or 1% chromatin decondensation produce a loss of about 1.5% surviving fraction. However, all the cell lines did not obey both correlations, suggesting that DSB repair and chromatin impairments contribute separately to increase the severity of DNA damage involved in cell lethality. Four cell lines groups showing different DSB repair and/or chromatin impairments were defined. Cell lines exhibiting both DSB repair defect and chromatin relaxation are the most radiosensitive. 相似文献
93.
Thierry Andre Philippe Colin Christophe Louvet Erik Gamelin Olivier Bouche Emmanuel Achille Nicolas Colbert Catherine Boaziz Pascal Piedbois Nicole Tubiana-Mathieu Arnaud Boutan-Laroze Michel Flesch Marc Buyse Aimery de Gramont 《Journal of clinical oncology》2003,21(15):2896-2903
PURPOSE: This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes' B2) and III (Dukes' C) colon cancer. PATIENTS AND METHODS: LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion. RESULTS: A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P =.74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P =.63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P =.18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P <.001). CONCLUSION: Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations. 相似文献
94.
Masahito Katoh Rick Wilmotte Marie-Claude Belkouch Nicolas de Tribolet Gianpaolo Pizzolato Pierre-Yves Dietrich 《Journal of neuro-oncology》2003,64(1):71-76
Survivin, a member of the inhibitor of apoptosis proteins gene family, was recently shown to be expressed by tumors originating from different cell lineages. There are also cumulative evidences that spontaneous immune response against survivin derived epitopes may occur. Here, using RT-PCR, Western-blot analysis and immunohistochemistry, we show that survivin is widely expressed by gliomas, meningiomas and schwannomas, both in vitro and in vivo. These data indicate that survivin may serve as an attractive target for immunotherapies designed for brain tumors. 相似文献
95.
Chango A Potier De Courcy G Boisson F Guilland JC Barbé F Perrin MO Christidès JP Rabhi K Pfister M Galan P Hercberg S Nicolas JP 《The British journal of nutrition》2000,84(6):891-896
The 677cytosine mutation identified in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been frequently associated with an elevated plasma homocysteine concentration. The aim of the present study was to determine the impact of this MTHFR common mutation on plasma and erythrocyte folate (RCF) and plasma total homocysteine (tHcy) concentrations in healthy French adults. A cohort of 291 subjects living in the Paris area and participating in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study were analysed to assess the impact of MTHFR polymorphism 677C-->T on folate status and plasma tHcy concentration. The frequency of the mutant homozygote for 677C-->T polymorphism (677TT genotype) in the present cohort was 16.8%. There were significant differences in plasma tHcy between 677CC, 677CT and 677TT genotype groups. The RCF concentrations were significantly different between each genotype, the lowest levels being associated with the 677TT genotype. When segregated by gender, no differences in tHcy between homozygous 677TT, heterozygous 677CT and wild-type 677CC genotype groups in women were observed. The fasting tHcy in women was unrelated to the 677C-->T mutation. However, tHcy was significantly increased in men with the homozygous 677TT genotype. We also analysed the possible implication of a second new MTHFR polymorphism (1298A-->C) in subjects with mild hyperhomocysteinaemia (4th quartile of homocysteinaemia; tHcy >11.1 micromol/l). The polymorphism 1298A-->C did not have a notable effect on tHcy or on the RCF levels. Our observations confirm a relatively high frequency of the 677TT genotype in the French population. Women with this genotype did not show the same increase in tHcy observed in men. In the present study dietary folate intake was not measured. Thus, the interaction of dietary folate with the MTHFR genotype in the French population needs further study. 相似文献
96.
Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids 总被引:5,自引:0,他引:5
The interaction between the estrogen receptor and a variety of flavonoids was studied in the presence or absence of estradiol using a stably-transfected human breast cancer cell line (MVLN). On the other hand, flavonoids were evaluated for their effects on proliferation in estrogen-dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. We established a relationship structure-activity and determined regions and/or substituents essential for estrogenic or antiestrogenic activities. In contrast, we did not find the same relationship for cell proliferation. Among all flavonoids used, only 7-methoxyflavanone and 7,8-dihydroxyflavone at high concentrations (50 μM) possess antiestrogenic and antiproliferative activities. These results suggest that two hydroxyls (in positions 7 and 8) or 7-methoxy substituents are essential for the antiestrogenic activity of flavonoids. However, it seems that flavonoids at high concentrations exert their antiproliferative activity through other estrogen receptor-independent mechanisms. 相似文献
97.
Victor Palomar-Asenjo Ma Soledad Boleas-Aguirre Noelia Sánchez-Ferrándiz Nicolas Perez Fernandez 《Otology & neurotology》2006,27(7):945-950
OBJECTIVES: To determine whether an association exists between the parameters of the caloric and rotatory chair tests in patients with unilateral Ménière's disease. METHODS: Patients with unilateral Ménière's disease (n = 100) were subjected to the caloric and the rotatory chair test (sinusoidal harmonic acceleration and impulsive tests) on the same day. Canal paresis and directional preponderance were assessed in the caloric test, and different variables were measured in the rotatory chair test based on the existence of abnormal parameters in the vestibulo-ocular reflex at two or three consecutive frequencies of those tested and on the time constant of the vestibulo-ocular reflex. STUDY DESIGN AND SETTING: A prospective study was conducted at a University hospital. RESULTS: An abnormal result in the caloric test was obtained from 73% of the patients. In the rotatory chair test, the most frequent abnormal findings involved increases in the normal phase lead at 2 consecutive frequencies tested (23%). There was a stronger association between an abnormal result in phase, gain, and/or symmetry at three adjacent frequencies and a pathological result in the caloric test. CONCLUSION: Very few of the criteria used to define the caloric and rotatory chair tests seem to be associated. This confirms previous knowledge that both tests examine vestibulo-ocular reflex by different ways. Only when vestibular dysfunction is severe enough (manifested by the finding of an abnormal result in at least three consecutive frequencies in the rotatory chair test), the caloric test is also found to be abnormal. 相似文献
98.
Nicolas Bourdel Horace Roman Guillaume Lebouedec Yann Lenglet Marie Accoceberry Michel Canis 《Gynecological surgery》2006,3(2):132-133
We report a case of postoperative Richter’s hernia presenting through a 5-mm sheath incision. A 58-year-old woman having undergone laparoscopic hysterectomy 8 days before presented with severe left abdominal pain, nausea and light-headedness. The hypothesis of a sigmoid volvulus was suggested based on peroperative rectum and sigmoid release, the X-ray finding, and pain evolution. A secondary laparoscopic procedure allowed both diagnosis of a Richter’s hernia through a 5-mm sheath incision and surgical repair of the hernia. The use of this sheath during the laparoscopic vagina suture caused extension of the wound. Large 5-mm sheath defect sufficient for a Richter’s hernia can be created by multiple passes with small instruments and require surgical closure at the end of laparoscopy. Laparoscopy is useful in cases of postoperative complications, particularly when other complementary examinations are less informative. 相似文献
99.
100.
Renaud Sabatier Ccile Vicier Sverine Garnier Arnaud Guille Nadine Carbuccia Nicolas Isambert Florence Dalenc Marie Robert Christelle Levy Jihane Pakradouni Jos Adelaïde Max Chaffanet Patrick Sfumato Emilie Mamessier Franois Bertucci Anthony Goncalves 《Molecular oncology》2022,16(10):2057
The phosphatidylinositol‐3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently activated in HER2‐negative breast cancer and may play a role in taxane resistance. The phase IB/II TAKTIC trial () has shown that combining a dual AKT and p70 ribosomal protein S6 kinase (p70S6K) inhibitor (LY2780301) taken orally with weekly paclitaxel in HER2‐negative advanced breast cancer is feasible, with preliminary evidence of efficacy. We wanted to explore whether circulating tumor DNA (ctDNA) may be a surrogate marker of treatment efficacy in this setting. Serial plasma samples were collected and cell‐free DNA was sequenced using low‐coverage whole‐genome sequencing, and analysis was completed with droplet digital polymerase chain reaction (PCR) for some patients with driver mutations. Baseline tumor fraction (TF) and TF after 7 weeks on treatment were compared to progression‐free survival (PFS) and the overall response rate. We also explored circulating copy number alterations associated with treatment failure. Of the 51 patients enrolled in the TAKTIC trial, at least one plasma sample was available for 44 cases (96 timepoints). All patients with tumor TP53, PI3KCA, or AKT1 mutations harbored at least one of these alterations in plasma. TF at inclusion was correlated with PFS (6m‐PFS was 92% for ctDNAneg patients vs 68% for ctDNApos cases; hazard ratio [HR] = 3.45, 95% confidence interval [CI] [1.34–8.90], P = 0.007). ctDNA status at week 7 was not correlated with prognosis. Even though most circulating copy number alterations were conserved at disease progression, some genomic regions of interest were altered in post‐progression samples. In conclusion, ctDNA detection at baseline was associated with shorter PFS in patients included in the TAKTIC trial. Plasma‐based copy number analysis may help to identify alterations involved in resistance to treatment. NCT01980277相似文献