首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2890篇
  免费   344篇
  国内免费   1篇
  2022年   30篇
  2021年   54篇
  2020年   51篇
  2019年   55篇
  2018年   80篇
  2017年   63篇
  2016年   108篇
  2015年   134篇
  2014年   165篇
  2013年   162篇
  2012年   198篇
  2011年   167篇
  2010年   147篇
  2009年   112篇
  2008年   135篇
  2007年   165篇
  2006年   141篇
  2005年   132篇
  2004年   141篇
  2003年   116篇
  2002年   113篇
  2001年   48篇
  2000年   50篇
  1999年   49篇
  1998年   38篇
  1997年   34篇
  1996年   24篇
  1995年   26篇
  1994年   31篇
  1993年   41篇
  1992年   45篇
  1991年   37篇
  1990年   36篇
  1989年   23篇
  1988年   27篇
  1987年   16篇
  1986年   27篇
  1985年   15篇
  1984年   16篇
  1983年   22篇
  1982年   22篇
  1981年   15篇
  1980年   16篇
  1979年   14篇
  1978年   12篇
  1977年   8篇
  1975年   10篇
  1974年   10篇
  1972年   10篇
  1971年   7篇
排序方式: 共有3235条查询结果,搜索用时 984 毫秒
91.
Red cusk-eel (Genypterus chilensis) is a native species with potential for Chilean aquaculture diversification. However, no information exists on the effects of temperature on oxidative stress and eggs quality markers in post-ovulatory eggs and ovary of this species. We determine that high and low temperature generate oxidative damage on post-ovulatory eggs, with no effect on ovary. Temperature induces thermal stress markers expression on post-ovulatory eggs, and modulates antioxidant and eggs quality markers on post-ovulatory eggs and ovary, information to consider for quality evaluation in the red cusk-eel management.  相似文献   
92.
As sessile organisms, plants are exposed to pathogen invasions and environmental fluctuations. To overcome the challenges of their surroundings, plants acquire the potential to sense endogenous and exogenous cues, resulting in their adaptability. Hence, plants have evolved a large collection of plasma membrane-resident receptors, including RECEPTOR-LIKE KINASEs(RLKs) and RECEPTOR-LIKE PROTEINs(RLPs) to perceive those signals and regulate plant growth,development, and immunity. The ability of RLKs and RLPs to recognize distinct ligands relies on diverse categories of extracellular domains evolved. Co-regulatory receptors are often required to associate with RLKs and RLPs to facilitate cellular signal transduction. RECEPTOR-LIKE CYTOPLASMIC KINASEs(RLCKs) also associate with the complex, bifurcating the signal to key signaling hubs, such as MITOGEN-ACTIVATED PROTEIN KINASE(MAPK) cascades, to regulate diverse biological processes. Here, we discuss recent knowledge advances in understanding the roles of RLKs and RLPs in plant growth, development, and immunity, and their connection with co-regulatory receptors, leading to activation of diverse intracellular signaling pathways.  相似文献   
93.
94.
With the aim of creating new bisubstrate inhibitors of protein farnesyltransferase (FTase), new carboxylic farnesyl pyrophosphate analogues have been designed and synthesized. The original structures are built around three elements: a prenyl moiety, a 1,4-diacid motif and an imidazole ring. All the compounds were evaluated for their ability to inhibit FTase and compared with the corresponding derivatives lacking the imidazole ring, synthesized for that purpose. These new compounds are not bisubstrate inhibitors probably because the imidazole ring is not in the right position to interact with the zinc atom. However these derivatives display FPP competitive inhibition with a good activity in the carboxylic farnesyl pyrophosphate analogues series.  相似文献   
95.
Metastatic carcinoma to the vulva is rare, where the incidence is believed to be between 5% and 8%.However, malignant tumors have been described in 3–11% of systemic scleroderma (SSc) cases.We report the case of one patient, a 66-year-old postmenopausal woman, whose medical history was marked with rheumatic vascular disease (systemic scleroderma) since 1993 without muscular, renal, cardiac lesions or HTA (arterial hypertension) and without tobacco history.The woman presented with a new vulvar mass of the right labia in December 2011 that had progressively enlarged in size.CT scan of the abdominopelvic region demonstrated a lobular mass of the right labia with central necrosis, 7 cm on the wide axis, and the rectum and the vaginal wall were normal. No inguinal or iliac lymphadenopathy was noted.An outpatient excisional biopsy revealed a poorly differentiated malignant tumor suggestive of carcinoma.IHC: CK7+/CK20−, estrogen receptors−, AE 1 AE 3+, vimentine+, S100−, Desmina−, CD34−, KI 67: 20%.The thoracic scan revealed a large mass of 4 cm × 3 cm in the right lung base with right paratracheal lymphadenopathy 3 cm × 2 cm.A bronchoscopy revealed discrete stenosis of the mediastinal portion of the right bronchial tree.The bronchial biopsy also revealed poorly differentiated lung carcinoma, non-small cell, which was identical with the vulvar tumor.

Conclusion

The presence of the single lung lesion with only one lymphadenopathy paratracheal with pathological and immunohistochemical (IHC) profile similar to the vulvar lesion, and a particular IHC profile with CK7+ and CK20− was detected – that is more specific to the primitive pulmonary cancer, and the presence of only one sarcoma marker vementine+, desmine and actine−. Also the presence of KI 67: 20%, predicted the proliferative and great metastatic power of the lung tumor was observed.Additionally, lung cancer was the most frequent type and may develop in scleroderma as reported in most studies.This allows to conclude for primitive lung carcinoma revealed with vulvar metastasis after elimination of the possibility of vulvar sarcoma.The patient was treated by chemotherapy (Taxol/Platin) with partial response from the lung after 3 cycles and palliative radiotherapy in the vulva with a good response.This case described primary lung carcinoma associated with scleroderma, revealed by a vulvar metastasis, which may be related to the aggressiveness of lung cancer when the lung fibrosis follow-up is not performed well to detect early the development of lung tumors in the patient with systemic scleroderma.  相似文献   
96.

Background

Baguio City, Philippines experienced its first influenza A(H1N1)pdm09 [A(H1)pdm09] case in May 2009. In spite of numerous reports describing the epidemiological and clinical features of A(H1)pdm09 cases, there are no studies about A(H1)pdm09 epidemiology in the Philippines, where year-round influenza activity was observed.

Objectives

We aimed to investigate the epidemiological and clinical features of A(H1)pdm09 in pandemic and post-pandemic periods.

Methods

Data were collected under enhanced surveillance of influenza-like illness (ILI) and severe acute respiratory infection (SARI) from January 2009 to December 2010. RT-PCR was used to detect A(H1)pdm09, following the protocol of the United States Centers for Disease Control and Prevention. The reproduction number was computed as a simple exponential growth rate. Differences in proportional and categorical data were examined using chi-square test or Fishers’ exact test.

Results and Conclusions

The outbreak was observed from week 25 to 35 in 2009 and from week 24 to 37 in 2010. The highest proportion of cases was among children aged 5–14 years. The number of ILI outpatients was 2.3-fold higher in 2009 than in 2010, while the number of inpatients was 1.8-fold higher in 2009. No significant difference in gender was observed during the two periods. The clinical condition of all patients was generally mild and self-limiting, with only 2 mortalities among inpatients in 2009. The basic reproduction number was estimated as 1.16 in 2009 and 1.05 in 2010 in the assumption of mean generation time as 2.6 days. School children played a significant role in facilitating influenza transmission.  相似文献   
97.

Background

Cacti establish mostly occurs under the canopy of nurse plants which provide a less stressful micro-environment, although mechanisms underlying this process are unknown. The impact of the combination of light and watering treatments on Opuntia streptacantha (Cactaceae) seedlings was examined.

Methods/Principal Findings

Ecophysiological [titratable acidity, osmotic potential (‘solute potential’, Ψs), relative growth rate (RGR) and their components (NAR, SLA, and LWR)], anatomical (chloroplast density, chloroplast frequency, and cell area), and environmental [photosynthetic photon flux density (PPFD) and air temperature] sets of variables were analyzed, assessing relationships between them and measuring the intensity of the relationships. Three harvests were carried out at days 15, 30, and 45. Ψs and acidity content were the most important responses for seedling establishment. The main anatomical and environmental variables were chloroplast density and water availability, respectively. Opuntia streptacantha seedlings establish better in the shade-watering treatment, due to higher Ψs and acidity, unaffected chloroplasts, and lower PPFD. In addition, the chloroplasts of cells under high-light and non-watering treatment were clumped closer to the center of the cytosol than those under shade-drought, to avoid photoinhibition and/or to better distribute or utilize the penetrating light in the green plant tissue.

Conclusions

Opuntia seedlings grow better under the shade, although they can tolerate drought in open spaces by increasing and moving chloroplasts and avoiding drastic decreases in their Ψs. This tolerance could have important implications for predicting the impact of climate change on natural desert regeneration, as well as for planning reforestation-afforestation practices, and rural land uses.  相似文献   
98.

Background

All four serotypes of dengue virus are endemic in Indonesia, where the population at risk for infection exceeds 200 million people. Despite continuous control efforts that were initiated more than four decades ago, Indonesia still suffers from multi-annual cycles of dengue outbreak and dengue remains as a major public health problem. Dengue vaccines have been viewed as a promising solution for controlling dengue in Indonesia, but thus far its potential acceptability has not been assessed.

Methodology/Principal Findings

We conducted a household survey in the city of Bandung, Indonesia by administering a questionnaire to examine (i) acceptance of a hypothetical pediatric dengue vaccine; (ii) participant''s willingness-to-pay (WTP) for the vaccine, had it not been provided for free; and (iii) whether people think vector control would be unnecessary if the vaccine was available. A proportional odds model and an interval regression model were employed to identify determinants of acceptance and WTP, respectively. We demonstrated that out of 500 heads of household being interviewed, 94.2% would agree to vaccinate their children with the vaccine. Of all participants, 94.6% were willing to pay for the vaccine with a median WTP of US$1.94. In addition, 7.2% stated that vector control would not be necessary had there been a dengue vaccination program.

Conclusions/Significance

Our results suggest that future dengue vaccines can have a very high uptake even when delivered through the private market. This, however, can be influenced by vaccine characteristics and price. In addition, reduction in community vector control efforts may be observed following vaccine introduction but its potential impact in the transmission of dengue and other vector-borne diseases requires further study.  相似文献   
99.

Background

The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS) may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF) diet.

Methods

C57BL/6 mice fed a HF diet (8 weeks) were treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis.

Results

All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM) gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression.

Conclusion

Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7) /Mas receptor axis and adiponectin levels.  相似文献   
100.
The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号