全文获取类型
收费全文 | 5193篇 |
免费 | 476篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 50篇 |
2021年 | 76篇 |
2020年 | 41篇 |
2019年 | 73篇 |
2018年 | 78篇 |
2017年 | 74篇 |
2016年 | 144篇 |
2015年 | 244篇 |
2014年 | 290篇 |
2013年 | 340篇 |
2012年 | 408篇 |
2011年 | 363篇 |
2010年 | 255篇 |
2009年 | 253篇 |
2008年 | 332篇 |
2007年 | 316篇 |
2006年 | 333篇 |
2005年 | 332篇 |
2004年 | 308篇 |
2003年 | 238篇 |
2002年 | 249篇 |
2001年 | 66篇 |
2000年 | 44篇 |
1999年 | 55篇 |
1998年 | 84篇 |
1997年 | 42篇 |
1996年 | 41篇 |
1995年 | 37篇 |
1994年 | 45篇 |
1993年 | 44篇 |
1992年 | 36篇 |
1991年 | 31篇 |
1990年 | 51篇 |
1989年 | 30篇 |
1988年 | 28篇 |
1987年 | 17篇 |
1986年 | 18篇 |
1985年 | 26篇 |
1984年 | 21篇 |
1983年 | 15篇 |
1982年 | 14篇 |
1981年 | 15篇 |
1980年 | 14篇 |
1979年 | 10篇 |
1978年 | 12篇 |
1976年 | 14篇 |
1974年 | 6篇 |
1973年 | 7篇 |
1971年 | 7篇 |
排序方式: 共有5670条查询结果,搜索用时 62 毫秒
951.
Frederik Staikowsky Fran?ois Talarmin Philippe Grivard Abdel Souab Isabelle Schuffenecker Karin Le Roux Marc Lecuit Alain Michault 《PloS one》2009,4(10)
Background
Chikungunya virus (CHIKV) is a recently re-emerged arthropod borne virus responsible for a massive outbreak in the Indian Ocean and India, and extended to Southeast Asia as well as Italy. CHIKV has adapted to Aedes albopictus, an anthropophilic mosquito species widely distributed in Asia, Europe, Africa and America. Our objective was to determine the clinical and biological features of patients at the acute phase of CHIKV infection.Methods and Findings
A prospective study enrolled 274 consecutive patients with febrile arthralgia recorded at the Emergency Department of the Groupe Hospitalier Sud-Réunion between March and May 2006. Three groups were defined: one group of 180 viremic patients (positive CHIKV RT-PCR), one group of 34 patients with acute post-viremic infection (negative CHIKV RT-PCR, positive anti-CHIKV IgM and negative IgG), and one group of 46 uninfected patients (negative CHIKV RT-PCR, anti-CHIKV IgM and IgG). Bivariate analyses of clinical and biological features between groups were performed. Patients with CHIKV viremia presented typically with asymmetrical bilateral polyarthralgia (96.5%) affecting the lower (98%) and small joints (74.8%), as well as asthenia (88.6%), headache (70%), digestive trouble (63.3%), myalgia (59%), exanthems (47.8%), conjunctival hyperhemia (23%) and adenopathy (8.9%). Vertigo, cutaneous dysesthesia, pharyngitis and haemorrhages were seldom observed. So far unreported symptoms such as chondrocostal arthralgia (20%), entesopathies (1.6%), talalgia (14%) were also noted. Prurit was less frequent during the viremic than post-viremic phase (13.9% vs. 41.2%; p<0.001), whereas lymphopenia was more frequent (87.6% vs. 39.4%; p<0.001). Others biological abnormalities included leukopenia (38.3%), thrombocytopenia (37.3%), increased ASAT and ALAT blood levels (31.6 and 7.3%, respectively) and hypocalcemia (38.7%). Lymphopenia <1,000/mm3 was very closely associated with viremic patients (Yule coefficient 0.82, positive predictive value 92.3%). Age under 65 was associated with a benign course, as no patients younger than 65 had to be hospitalized (Yule coefficient 0.78).Conclusions
The diagnosis of CHIKV infection in acute phase is based on commonly accepted clinical criteria (fever and arthralgia), however clinical and biological diffrences exist in acute phase depending on whether or not the patient is within the viremic phase of the infection. 相似文献952.
Gabriella Eliason Samy M Abdel-Halim Karin Piehl-Aulin Fawzi Kadi 《Respiratory research》2010,11(1):97
Background
It is hypothesized that decreased capillarization of limb skeletal muscle is implicated in the decreased exercise tolerance in COPD patients. We have recently demonstrated decreased number of capillaries per muscle fibre (CAF) but no changes in CAF in relation to fibre area (CAFA), which is based on the diffusion distance between the capillary and muscle fibre. The aim of the current study is to investigate the muscle-to-capillary interface which is an important factor involved in oxygen supply to the muscle that has previously been suggested to be a more sensitive marker for changes in the capillary bed compared to CAF and CAFA.Methods
23 COPD patients and 12 age-matched healthy subjects participated in the study. Muscle-to-capillary interface was assessed in muscle biopsies from the tibialis anterior muscle using the following parameters:1) The capillary-to-fibre ratio (C:Fi) which is defined as the sum of the fractional contributions of all capillary contacts around the fibre2) The ratio between C:Fi and the fibre perimeter (CFPE-index)3) The ratio between length of capillary and fibre perimeter (LC/PF) which is also referred to as the index of tortuosity.Exercise capacity was determined using the 6-min walking test.Results
A positive correlation was found between CFPE-index and ascending disease severity with CFPE-index for type I fibres being significantly lower in patients with moderate and severe COPD. Furthermore, a positive correlation was observed between exercise capacity and CFPE-index for both type I and type IIa fibres.Conclusion
It can be concluded that the muscle-to-capillary interface is disturbed in the tibialis anterior muscle in patients with COPD and that interface is strongly correlated to increased disease severity and to decreased exercise capacity in this patient group. 相似文献953.
954.
Ann-Charlotte Johansson Hanna Appelqvist Cathrine Nilsson Katarina Kågedal Karin Roberg Karin Öllinger 《Apoptosis : an international journal on programmed cell death》2010,15(5):527-540
Lysosomal membrane permeabilization (LMP) occurs in response to a large variety of cell death stimuli causing release of cathepsins
from the lysosomal lumen into the cytosol where they participate in apoptosis signaling. In some settings, apoptosis induction
is dependent on an early release of cathepsins, while under other circumstances LMP occurs late in the cell death process
and contributes to amplification of the death signal. The mechanism underlying LMP is still incompletely understood; however,
a growing body of evidence suggests that LMP may be governed by several distinct mechanisms that are likely engaged in a death
stimulus- and cell-type-dependent fashion. In this review, factors contributing to permeabilization of the lysosomal membrane
including reactive oxygen species, lysosomal membrane lipid composition, proteases, p53, and Bcl-2 family proteins, are described.
Potential mechanisms to safeguard lysosomal integrity and confer resistance to lysosome-dependent cell death are also discussed. 相似文献
955.
Ulf Granhall Allana Welsh Ingela Noredal Throbäck Karin Hjort Mikael Hansson Sara Hallin 《Journal of industrial microbiology & biotechnology》2010,37(10):1061-1069
Paper mills processing recycled paper suffer from biofouling causing problems both in the mill and final product. The total
bacterial community composition and identification of specific taxa in the process water and biofilms at the stock preparation
and paper machine areas in a mill with recycled paper pulp was described by using a DNA-based approach. Process water in a
similar mill was also analyzed to investigate if general trends can be found between mills and over time. Bacterial community
profiles, analyzed by terminal-restriction fragment length polymorphism (T-RFLP), in process water showed that the dominant
peaks in the profiles were similar between the two mills, although the overall composition was unique for each mill. When
comparing process water and biofilm at different locations within one of the mills, we observed a separation according to
location and sample type, with the biofilm from the paper machine being most different. 16S rRNA gene clone libraries were
generated and 404 clones were screened by RFLP analysis. Grouping of RFLP patterns confirmed that the biofilm from the paper
machine was most different. A total of 99 clones representing all RFLP patterns were analyzed, resulting in sequences recovered
from nine bacterial phyla, including two candidate phyla. Bacteroidetes represented 45% and Actinobacteria 23% of all the
clones. Sequences with similarity to organisms implicated in biofouling, like Chryseobacterium spp. and Brevundimonas spp., were recovered from all samples even though the mill had no process problems during sampling, suggesting that they
are part of the natural paper mill community. Moreover, many sequences showed little homology to as yet uncultivated bacteria
implying that paper mills are interesting for isolation of new organisms, as well as for bioprospecting. 相似文献
956.
Optimal conditions for the extraction of casearins from Casearia sylvestris were determined using response surface methodology. The maceration and sonication extraction techniques were performed using a 3 x 3 x 3 full factorial design including three acidity conditions, three solvents of different polarities and three extraction times. The yields and selectivities of the extraction of casearins were significantly influenced by acidity conditions. Taking into account all variables tested, the optimal conditions for maceration extraction were estimated to involve treatment with dichloromethane saturated with ammonium hydroxide for 26 h. Similar yields and selectivities for casearins were determined for sonication extraction using the same solvent but for the much shorter time of 1 h. The best results for stabilisation of the fresh plant material were obtained using leaves that had been oven dried at 40 degrees C for 48 h. 相似文献
957.
Annika K. Jägerbrand Karin E. M. Lindblad Robert G. Björk Juha M. Alatalo Ulf Molau 《Biodiversity and Conservation》2006,15(14):4453-4475
Effects of simulated environmental change on bryophyte and lichen species richness and diversity in alpine tundra were investigated
in a 5-year experiment at Latnjajaure, northern Sweden. The experiment had a factorial design including fertilisation and
temperature enhancement in one meadow and one heath plant community. Responses in species richness, biodiversity, and species
composition of bryophytes and lichens to experimental treatments were compared to the observed variation in six naturally
occurring plant communities. The combination of fertilisation and enhanced temperature resulted in a species impoverishment,
for bryophytes in the bryophyte-dominated community, and for lichens in the lichen-dominated communities, but the species
composition stayed within the observed natural variation. During the course of the study, no species new to the investigated
mid-alpine landscape were recorded, but that scenario is realistic within a decade when comparing with the processes seen
in vascular plants. 相似文献
958.
Kuklish SL Backer RT Briner K Doecke CW Husain S Mullaney JT Ornstein PL Zgombick JM O'Brien TP Fisher MJ 《Bioorganic & medicinal chemistry letters》2006,16(14):3843-3846
Homologation and cyclization back to the chiral methine of compound 3 yields achiral 4,4-disubstituted piperidine privileged structures (e.g., 8a) useful in the construction of melanocortin 4 receptor (MC4R) ligands. The piperidine nitrogen was replaced with carbon, oxygen, sulfur, and sulfone with minor erosion of binding. The methyl cyclohexane substituent was the most potent while significant affinity was still seen for smaller lipophilic groups such as ethyl. 相似文献
959.
Garcia Collazo AM Koehler KF Garg N Färnegårdh M Husman B Ye L Ljunggren J Mellström K Sandberg J Grynfarb M Ahola H Malm J 《Bioorganic & medicinal chemistry letters》2006,16(5):1240-1244
Based on the examination of the crystal structure of rat TRbeta complexed with 3,5,3'-triiodo-l-thyronine (2) a novel TRbeta-selective indole derivative 6b was prepared and tested in vitro. This compound was found to be 14 times selective for TRbeta over TRalpha in binding and its beta-selectivity could be rationalized through the comparison of the X-ray crystallographic structures of 6b complexed with TRalpha and TRbeta. 相似文献
960.
Ward EJ Shcherbata HR Reynolds SH Fischer KA Hatfield SD Ruohola-Baker H 《Current biology : CB》2006,16(23):2352-2358
Stem cells are maintained and retain their capacity to continue dividing because of the influence of a niche. Although niches are important to maintain "stemness" in a wide variety of tissues, control of these niches is poorly understood. The Drosophila germline stem cells (GSCs) reside in a somatic cell niche. We show that Notch activation can induce the expression of niche-cell markers even in an adult fly; overexpression of Delta in the germline, or activated Notch in the somatic cells, results in extra niche cells, up to 10-fold over the normal number. In turn, these ectopic niche cells induce ectopic GSCs. Conversely, when GCSs do not produce functional Notch ligands, Delta and Serrate, the TGF-beta pathway is not activated in the GSCs, and they differentiate and subsequently leave the niche. Importantly, clonal analysis reveals that the receiving end of the Notch pathway is required in the somatic cells. These data show that a feedback loop exists between the stem cells and niche cells. Demonstration that stem cells can contribute to niche function has far-reaching consequences for stem cell therapies and may provide insight into how cancer can spread throughout an organism via populations of cancer stem cells. 相似文献