全文获取类型
收费全文 | 3036篇 |
免费 | 180篇 |
国内免费 | 1篇 |
专业分类
3217篇 |
出版年
2024年 | 7篇 |
2023年 | 29篇 |
2022年 | 61篇 |
2021年 | 120篇 |
2020年 | 77篇 |
2019年 | 83篇 |
2018年 | 97篇 |
2017年 | 83篇 |
2016年 | 115篇 |
2015年 | 189篇 |
2014年 | 179篇 |
2013年 | 234篇 |
2012年 | 268篇 |
2011年 | 252篇 |
2010年 | 156篇 |
2009年 | 134篇 |
2008年 | 149篇 |
2007年 | 181篇 |
2006年 | 165篇 |
2005年 | 144篇 |
2004年 | 142篇 |
2003年 | 98篇 |
2002年 | 91篇 |
2001年 | 21篇 |
2000年 | 12篇 |
1999年 | 16篇 |
1998年 | 26篇 |
1997年 | 12篇 |
1996年 | 8篇 |
1995年 | 8篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 3篇 |
1991年 | 12篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1971年 | 2篇 |
排序方式: 共有3217条查询结果,搜索用时 0 毫秒
51.
M. Gabriela Mángano Noelia B. Carmona Luis A. Buatois Fernando Muñiz Guinea 《Ichnos》2013,20(3):179-190
A new ichnospecies of Arthrophycus Hall 1852, A. minimus , is described from Upper Cambrian-Lower Tremadocian, shallow-marine strata of northwest Argentina. This new ichnospecies consists of small, long, regularly annulated hypichnial elements displaying subcircular to squarish cross-section and a ventral median groove. Side branches are occasionally present, but palmate, fan-like structures and scribbling patterns are absent. We adopt a relatively narrow diagnosis of Arthrophycus , suggesting that roughly annulated, cylindrical structures should not be included in this ichnogenus, unless other diagnostic features (i.e., squarish cross-section, median groove, zipper-like annulations) are also present. Arthrophycus is a common ichnotaxon in Ordovician-Silurian shallow-marine siliciclastic environments. Post-Paleozoic occurrences are removed from Arthrophycus . Arthrophycus has been proposed as a biostratigraphic index fossil in Ordovician-Silurian rocks. The presence of A. minimus in the Santa Rosita Formation of northwest Argentina indicates that Arthrophycus ranges at least from the Upper Cambrian-Lower Tremadocian with probable representatives in the Lower Cambrian and, therefore, its biostratigraphic utility is extended. Arthrophycus minimus represents the first Cambrian occurrence exhibiting not only fine, diagnostic morphologic features, but also the classical Arthrophycus behavioral pattern in dense monoichnospecific assemblages. The exploratory behavioral pattern displayed by A. minimus is simpler than that of the younger ichnospecies, particularly A. brogniartii, A. alleghaniensis, and A. lateralis . This is consistent with the basal position of A. minimus within the arthrophycid lineage. 相似文献
52.
The short- and long-term pro-oxidant effect of protoporphyrin IX (PROTO) administration to mice was studied in liver. A peak of liver porphyrin accumulation was found 2 h after the injection of PROTO (3.5 mg/kg, i.p.); then the amount of porphyrins diminished due to biliar excretion. After several doses of PROTO (1 dose every 24 h up to 5 doses) a sustained enhancement of liver porphyrins was observed. The activity of δ-amino-levulinic acid synthetase was induced 70–90% over the control values 4 h after the first injection of PROTO and stayed at these high levels throughout the period of the assay. Administration of PROTO induced rapid liver damage, involving lipid peroxidation. Hepatic GSH content was increased 2 h after the first injection of PROTO, but then decreased below the control values which were maintained after several doses of porphyrin. After a single dose of PROTO, Cu-Zn superoxide dismutase (SOD) was rapidly induced, suggesting that superoxide radicals had been generated. Increased levels of hydrogen peroxide coming from the reaction catalyzed by SOD and lipid peroxides as a consequence of membrane peroxidation, induced the activity of catalase and glutathione peroxidase (GPx), while decreased GSH levels induced glutathione reductase (GRed) activity. However after 5 doses of PROTO, the activity of SOD was reduced reaching control values. GPx and catalase activities slowly went down, while GRed continued increasing as long as the levels of GSH were kept very low. TBARS values, although lower than those observed after a single dose of PROTO, remained above control values; Glutathione S-transferase activity was instead greatly diminished, indicating sustained liver damage.Our findings would indicate that accumulation of PROTO in liver induces oxidative stress, leading to rapid increase in the activity of the antioxidant enzymes to avoid or revert liver damage. However, constant accumulation of porphyrins provokes a liver damage so severe that the antioxidant system is compromised. 相似文献
53.
54.
Olivia Weigert Caroline von Spee Reinmar Undeutsch Lutz Kloke Jens Y Humrich Gabriela Riemekasten 《Arthritis research & therapy》2013,15(1):R35
Introduction
The ability to ameliorate murine lupus renders regulatory T cells (Treg) a promising tool for the treatment of systemic lupus erythematosus (SLE). In consideration to the clinical translation of a Treg-based immunotherapy of SLE, we explored the potential of CD4+Foxp3+ Treg to maintain disease remission after induction of remission with an established cyclophosphamide (CTX) regimen in lupus-prone (NZBxNZW) F1 mice. As a prerequisite for this combined therapy, we also investigated the impact of CTX on the biology of endogenous Treg and conventional CD4+ T cells (Tcon).Methods
Remission of disease was induced in diseased (NZBxNZW) F1 mice with an established CTX regimen consisting of a single dose of glucocorticosteroids followed by five day course with daily injections of CTX. Five days after the last CTX injection, differing amounts of purified CD4+Foxp3+CD25+ Treg were adoptively transferred and clinical parameters, autoantibody titers, the survival and changes in peripheral blood lymphocyte subsets were determined at different time points during the study. The influence of CTX on the numbers, frequencies and proliferation of endogenous Treg and Tcon was analyzed in lymphoid organs by flow cytometry.Results
Apart from abrogating the proliferation of Tcon, we found that treatment with CTX induced also a significant inhibition of Treg proliferation and a decline in Treg numbers in lymphoid organs. Additional adoptive transfer of 1.5 × 106 purified Treg after the CTX regimen significantly increased the survival and prolonged the interval of remission by approximately five weeks compared to mice that received only the CTX regimen. The additional clinical amelioration was associated with an increase in the Treg frequency in the peripheral blood indicating a compensation of CTX-induced Treg deficiency by the Treg transfer.Conclusions
Treg were capable to prolong the interval of remission induced by conventional cytostatic drugs. This study provides valuable information and a first proof-of-concept for the feasibility of a Treg-based immunotherapy in the maintenance of disease remission in SLE. 相似文献55.
Jennifer L Barton Gabriela Schmajuk Laura Trupin Jonathan Graf John Imboden Edward H Yelin Dean Schillinger 《Arthritis research & therapy》2013,15(5):R157
Introduction
Our objective was to determine rheumatoid arthritis (RA) patients’ understanding of methotrexate and assess whether knowledge varies by age, education, English language proficiency, or other disease-related factors.Methods
Adults with RA (n = 135) who were enrollees of an observational cohort completed a structured telephone interview in their preferred language between August 2007 and July 2009. All subjects who reported taking methotrexate were asked 11 questions about the medication in addition to demographics, education level, and language proficiency. Primary outcome was a total score below the 50th percentile (considered inadequate methotrexate knowledge). Bivariable and multivariable logistic regressions were performed. Covariates included demographics, language proficiency, education, and disease characteristics.Results
Of 135 subjects, 83% were female, with a mean age of 55 ± 14 years. The majority spoke English (64%), followed by 22% Spanish and 14% Cantonese or Mandarin. Limited English language proficiency (LEP) was reported in 42%. Mean methotrexate knowledge score was 5.4 ± 2.6 (range, 0 to 10); 73 (54%) had a score lower than 5 (of 10). Age older than 55, less than high school education, LEP, better function, and biologic use were independently associated with poor knowledge.Conclusions
In a diverse RA cohort, overall methotrexate knowledge was poor. Older age and limited proficiency in English were significant correlates of poor knowledge. Identification of language barriers and improved clinician-patient communication around methotrexate dosing and side effects may lead to improved safety and enhanced benefits of this commonly used RA medication. 相似文献56.
Dasfne Lee‐Liu Gabriela Edwards‐Faret Víctor S. Tapia Juan Larraín 《Genesis (New York, N.Y. : 2000)》2013,51(8):529-544
Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative‐permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow regeneration. This comparison should lead us toward finding how to promote regeneration in organisms that are unable to do so. genesis 51:529–544. © 2013 Wiley Periodicals, Inc. 相似文献
57.
58.
Simon Rinaldi Kathryn M. Brennan Gabriela Kalna Christa Walgaard Pieter van Doorn Bart C. Jacobs Robert K. Yu Jan-Eric Mansson Carl S. Goodyear Hugh J. Willison 《PloS one》2013,8(12)
Autoantibodies are infrequently detected in the sera of patients with the demyelinating form of Guillain-Barré syndrome most commonly encountered in the Western world, despite abundant circumstantial evidence suggesting their existence. We hypothesised that antibody specificities reliant on the cis interactions of neighbouring membrane glycolipids could explain this discrepancy, and would not have been detected by traditional serological assays using highly purified preparations of single gangliosides. To assess the frequency of glycolipid complex antibodies in a Western European cohort of patients GBS we used a newly developed combinatorial glycoarray methodology to screen against large range of antigens (11 gangliosides, 8 other single glycolipids and 162 heterodimeric glycolipid complexes). Serum samples of 181 patients from a geographically defined, Western European cohort of GBS cases were analysed, along with 161 control sera. Serum IgG binding to single gangliosides was observed in 80.0% of axonal GBS cases, but in only 11.8% of cases with demyelinating electrophysiology. The inclusion of glycolipid complexes increased the positivity rate in demyelinating disease to 62.4%. There were 40 antigens with statistically significantly increased binding intensities in GBS as compared to healthy control sera. Of these, 7 complex antigens and 1 single ganglioside also produced statistically significantly increased binding intensities in GBS versus neurological disease controls. The detection of antibodies against specific complexes was associated with particular clinical features including disease severity, requirement for mechanical ventilation, and axonal electrophysiology. This study demonstrates that while antibodies against single gangliosides are often found in cases with axonal-type electrophysiology, antibodies against glycolipid complexes predominate in cases with demyelinating electrophysiology, providing a more robust serum biomarker than has ever been previously available for such cases. This work confirms the activation of the humoral immune system in the dysimmune disease process in GBS, and correlates patterns of antigen recognition with different clinical features. 相似文献
59.
Camila Gewehr Sara Marchesan Oliveira Mateus Fortes Rossato Gabriela Trevisan Gerusa Duarte Dalmolin Flávia Karine Rigo Célio José de Castro Júnior Marta Nascimento Cordeiro Juliano Ferreira Marcus V. Gomez 《PLoS neglected tropical diseases》2013,7(4)
Background
The frequency of accidental spider bites in Brazil is growing, and poisoning due to bites from the spider genus Phoneutria nigriventer is the second most frequent source of such accidents. Intense local pain is the major symptom reported after bites of P. nigriventer, although the mechanisms involved are still poorly understood. Therefore, the aim of this study was to identify the mechanisms involved in nociception triggered by the venom of Phoneutria nigriventer (PNV).Methodology/Principal Findings
Twenty microliters of PNV or PBS was injected into the mouse paw (intraplantar, i.pl.). The time spent licking the injected paw was considered indicative of the level of nociception. I.pl. injection of PNV produced spontaneous nociception, which was reduced by arachnid antivenin (ArAv), local anaesthetics, opioids, acetaminophen and dipyrone, but not indomethacin. Boiling or dialysing the venom reduced the nociception induced by the venom. PNV-induced nociception is not dependent on glutamate or histamine receptors or on mast cell degranulation, but it is mediated by the stimulation of sensory fibres that contain serotonin 4 (5-HT4) and vanilloid receptors (TRPV1). We detected a kallikrein-like kinin-generating enzyme activity in tissue treated with PNV, which also contributes to nociception. Inhibition of enzymatic activity or administration of a receptor antagonist for kinin B2 was able to inhibit the nociception induced by PNV. PNV nociception was also reduced by the blockade of tetrodotoxin-sensitive Na+ channels, acid-sensitive ion channels (ASIC) and TRPV1 receptors.Conclusion/Significance
Results suggest that both low- and high-molecular-weight toxins of PNV produce spontaneous nociception through direct or indirect action of kinin B2, TRPV1, 5-HT4 or ASIC receptors and voltage-dependent sodium channels present in sensory neurons but not in mast cells. Understanding the mechanisms involved in nociception caused by PNV are of interest not only for better treating poisoning by P. nigriventer but also appreciating the diversity of targets triggered by PNV toxins. 相似文献60.