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961.
Tamer M. A. Mohamed Delvac Oceandy Sukhpal Prehar Nasser Alatwi Zeinab Hegab Florence M. Baudoin Adam Pickard Aly O. Zaki Raja Nadif Elizabeth J. Cartwright Ludwig Neyses 《The Journal of biological chemistry》2009,284(18):12091-12098
The cardiac neuronal nitric-oxide synthase (nNOS) has been described as a
modulator of cardiac contractility. We have demonstrated previously that
isoform 4b of the sarcolemmal calcium pump (PMCA4b) binds to nNOS in the heart
and that this complex regulates β-adrenergic signal transmission in
vivo. Here, we investigated whether the nNOS-PMCA4b complex serves as a
specific signaling modulator in the heart. PMCA4b transgenic mice (PMCA4b-TG)
showed a significant reduction in nNOS and total NOS activities as well as in
cGMP levels in the heart compared with their wild type (WT) littermates. In
contrast, PMCA4b-TG hearts showed an elevation in cAMP levels compared with
the WT. Adult cardiomyocytes isolated from PMCA4b-TG mice demonstrated a
3-fold increase in Ser16 phospholamban (PLB) phosphorylation as
well as Ser22 and Ser23 cardiac troponin I (cTnI)
phosphorylation at base line compared with the WT. In addition, the relative
induction of PLB phosphorylation and cTnI phosphorylation following
isoproterenol treatment was severely reduced in PMCA4b-TG myocytes, explaining
the blunted physiological response to the β-adrenergic stimulation. In
keeping with the data from the transgenic animals, neonatal rat cardiomyocytes
overexpressing PMCA4b showed a significant reduction in nitric oxide and cGMP
levels. This was accompanied by an increase in cAMP levels, which led to an
increase in both PLB and cTnI phosphorylation at base line. Elevated cAMP
levels were likely due to the modulation of cardiac phosphodiesterase, which
determined the balance between cGMP and cAMP following PMCA4b overexpression.
In conclusion, these results showed that the nNOS-PMCA4b complex regulates
contractility via cAMP and phosphorylation of both PLB and cTnI.Neuronal nitric-oxide synthase
(nNOS)5 is involved in
a number of key processes in cardiomyocytes including calcium cycling
(1), the β-adrenergic
contractile response (2,
3), post-infarct left
ventricular remodeling (4), and
the regulation of redox equilibrium
(5). Moreover, a polymorphism
in an nNOS-interacting protein, CAPON, has been found to form a quantitative
trait for the determination of the QT interval in humans
(6), whereas a mutation in
α1-syntrophin (SNTA1), another interacting partner of nNOS, has been
associated with long QT syndrome
(7). The signaling events
downstream of the nNOS-CAPON
(8) and nNOS-SNTA1
(7) complexes, which are
responsible for mediating cardiac repolarization and sodium current
respectively, have been elucidated. The nNOS-containing protein complex is
therefore of immediate relevance to human pathology.In recent years, we have shown that the sarcolemmal calcium pump, which
ejects calcium to the extracellular compartment (reviewed in Refs.
9 and
10), is an important molecule
involved in signal regulation and transmission in the heart
(11). We have demonstrated
that isoform 4b of the sarcolemmal calcium pump (also known as PMCA4b for
plasma membrane calcium/calmodulin-dependent
ATPase 4b) modulates signaling through a tight molecular
interaction with nNOS, leading to the modulation of β-adrenergic
responsiveness in the heart
(12). However, the events
following signaling through the PMCA4b-nNOS complex remain unknown.In myocardial cells, nNOS has been localized to the sarcolemma
(13), sarcoplasmic reticulum
(2), and mitochondria
(14), and translocation
between compartments has been demonstrated
(15). It has been speculated
that these various localizations provide specificity to NO signaling, but the
exact mechanisms have yet to be elucidated. In this study, we show a mechanism
by which one fraction of nNOS serves highly specific functions through binding
to PMCA4b. As PMCA4b is confined to the sarcolemma and is a calcium pump, it
is the first identified protein to fulfill these aggregate functions. 1) It
acts as an anchoring protein; 2) it regulates nNOS activity; and 3) it
modulates a process at the plasma membrane, i.e. β-adrenergic
signaling. 相似文献
962.
Hanene Medini Ameur Elaissi Farhat Farhat Mohamed Larbi Khouja Rachid Chemli Fathia Harzallah‐Skhiri 《化学与生物多样性》2009,6(9):1378-1387
The essential‐oil composition of 60 individual trees of Juniperus phoenicea L. from four Tunisian populations in three different periods were investigated by GC and GC/MS analyses. 59 Compounds were identified in the oils, and a relatively high variation in their contents was found. All the oils were dominated by the terpenic hydrocarbon fraction, and the main component was α‐pinene (20.28–40.86%). The results of the oil compositions were processed by hierarchical clustering and principal component analysis (PCA) allowing establishing four groups of essential‐oils differentiated by one compound or more. Pattern of geographic variation in essential‐oil composition indicated that individuals from the continental site (Makthar) were clearly distinguished from those from littoral localities (Tabarka, Hawaria, and Rimel). 相似文献
963.
Histopathological effects of cisplatin,doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats
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Hassan I El-Sayyad Mohamed F Ismail F M Shalaby RF Abou-El-Magd Rajiv L Gaur Augusta Fernando Madhwa HG Raj Allal Ouhtit 《International journal of biological sciences》2009,5(5):466-473
Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs. 相似文献
964.
965.
Sylvanne M Daniels Carlos E Melendez-Peña Robert J Scarborough Aïcha Daher Helen S Christensen Mohamed El Far Damian FJ Purcell Sébastien Lainé Anne Gatignol 《BMC molecular biology》2009,10(1):38-13
Background
Dicer, Ago2 and TRBP are the minimum components of the human RNA-induced silencing complex (RISC). While Dicer and Ago2 are RNases, TRBP is the double-stranded RNA binding protein (dsRBP) that loads small interfering RNA into the RISC. TRBP binds directly to Dicer through its C-terminal domain. 相似文献966.
Mariam Siala Radhouane Gdoura Hela Fourati Markus Rihl Benoit Jaulhac Mohamed Younes Jean Sibilia Sofien Baklouti Naceur Bargaoui Slaheddine Sellami Abdelghani Sghir Adnane Hammami 《Arthritis research & therapy》2009,11(4):R102
Introduction
Broad-range rDNA PCR provides an alternative, cultivation-independent approach for identifying bacterial DNA in reactive and other form of arthritis. The aim of this study was to use broad-range rDNA PCR targeting the 16S rRNA gene in patients with reactive and other forms of arthritis and to screen for the presence of DNA from any given bacterial species in synovial fluid (SF) samples.Methods
We examined the SF samples from a total of 27 patients consisting of patients with reactive arthritis (ReA) (n = 5), undifferentiated arthritis (UA) (n = 9), rheumatoid arthritis (n = 7), and osteoarthritis (n = 6) of which the latter two were used as controls. Using broad-range bacterial PCR amplifying a 1400 bp fragment from the 16S rRNA gene, we identified and sequenced at least 24 clones from each SF sample. To identify the corresponding bacteria, DNA sequences were compared to the EMBL (European Molecular Biology Laboratory) database.Results
Bacterial DNA was identified in 20 of the 27 SF samples (74, 10%). Analysis of a large number of sequences revealed the presence of DNA from more than one single bacterial species in the SF of all patients studied. The nearly complete sequences of the 1400 bp were obtained for most of the detected species. DNA of bacterial species including Shigella species, Escherichia species, and other coli-form bacteria as well as opportunistic pathogens such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans were shared in all arthritis patients. Among pathogens described to trigger ReA, DNA from Shigella sonnei was found in ReA and UA patients. We also detected DNA from rarely occurring human pathogens such as Aranicola species and Pantoea ananatis. We also found DNA from bacteria so far not described in human infections such as Bacillus niacini, Paenibacillus humicus, Diaphorobacter species and uncultured bacterium genera incertae sedis OP10.Conclusions
Broad-range PCR followed by cloning and sequencing the entire 16S rDNA, allowed the identification of the bacterial DNA environment in the SF samples of arthritic patients. We found a wide spectrum of bacteria including those known to be involved in ReA and others not previously associated with arthritis. 相似文献967.
Ashraf M Shoma Madiha H Mohamed Nashaat Nouman Mahmoud Amin Ibtihal M Ibrahim Salwa S Tobar Hanan E Gaffar Warda F Aboelez Salwa E Ali Soheir G William 《World journal of surgical oncology》2009,7(1):1-10
Background
Proximal major limb amputations due to malignant tumors have become rare but are still a valuable treatment option in palliation and in some cases can even cure. The aim of this retrospective study was to analyse outcome in those patients, including the postoperative course, survival, pain, quality of life, and prosthesis usage.Methods
Data of 45 consecutive patients was acquired from patient's charts and contact to patients, and general practitioners. Patients with interscapulothoracic amputation (n = 14), shoulder disarticulation (n = 13), hemipelvectomy (n = 3) or hip disarticulation (n = 15) were included.Results
The rate of proximal major limb amputations in patients treated for sarcoma was 2.3% (37 out of 1597). Survival for all patients was 42.9% after one year and 12.7% after five years. Survival was significantly better in patients with complete tumor resections. Postoperative chemotherapy and radiation did not prolong survival. Eighteen percent of the patients with malignant disease developed local recurrence. In 44%, postoperative complications were observed. Different modalities of postoperative pain management and the site of the amputation had no significant influence on long-term pain assessment and quality of life. Eighty-seven percent suffered from phantom pain, 15.6% considered their quality of life worse than before the operation. Thirty-two percent of the patients who received a prosthesis used it regularly.Conclusion
Proximal major limb amputations severely interfere with patients' body function and are the last, albeit valuable, option within the treatment concept of extremity malignancies or severe infections. Besides short survival, high complication rates, and postoperative pain, patients' quality of life can be improved for the time they have remaining. 相似文献968.
Hadda TB Akkurt M Baba MF Daoudi M Bennani B Kerbal A Chohan ZH 《Journal of enzyme inhibition and medicinal chemistry》2009,24(2):457-463
A series of nine polypyridyl-ruthenium (II) complexes (N-ligands = 2,2'-bipyridines; 2,2'-6',2'-terpyridines, di-alkyloxy-2,2'-6,2-bipyridine-3,3'-di-carboxylates), were tested against Mycobacterium tuberculosis (MBT). The complex (11) showed remarkable activity against MBT as compared to other complexes, (1-10). The aquo ligand of complex (11), as opposed to other chloro and acetonitrile derivatives, appears to play a key role in the antitubercular potency of this new class of metal-based compounds. 相似文献
969.
Nadir Chabane Nadia Zayed Mohamed Benderdour Johanne Martel-Pelletier Jean-Pierre Pelletier Nicolas Duval Hassan Fahmi 《Arthritis research & therapy》2009,11(2):1-12
Introduction
Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.Methods
Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.Results
The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.Conclusions
Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors. 相似文献970.
Alia A. Badawi Samia A. Nour Wedad S. Sakran Shereen Mohamed Sameh El-Mancy 《AAPS PharmSciTech》2009,10(4):1081-1084
Microemulsions (MEs) are clear, thermodynamically stable systems. They were used to solubilize drugs and to improve topical
drug availability. Salicylic acid (SA) is a keratolytic agent used in topical products with antimicrobial actions. The objective
of this work was to prepare and evaluate SA ME systems. Different concentrations of SA were incorporated in an ME base composed
of isopropyl myristate, water, and Tween 80: propylene glycol in the ratio of 15:1. Three ME systems were prepared: S2%, S5%, and S10% which contain 2%, 5%, and 10% of SA, respectively. Evaluation by examination under cross-polarizing microscope, measuring
of percent transmittance, pH measurement, determination of the specific gravity, assessment of rheological properties, and
accelerated stability study were carried out. The data showed that the addition of SA markedly affected the physical properties
of the base. All systems were not affected by accelerated stability tests. Stability study for 6 months under ambient conditions
was carried out for S10%. No remarkable changes were recorded except a decrease in the viscosity value after 1 month. The results suggested that ME
could be a suitable vehicle for topical application of different concentrations of SA. 相似文献