全文获取类型
收费全文 | 3446篇 |
免费 | 236篇 |
国内免费 | 253篇 |
专业分类
3935篇 |
出版年
2024年 | 7篇 |
2023年 | 43篇 |
2022年 | 109篇 |
2021年 | 193篇 |
2020年 | 126篇 |
2019年 | 153篇 |
2018年 | 163篇 |
2017年 | 103篇 |
2016年 | 131篇 |
2015年 | 190篇 |
2014年 | 257篇 |
2013年 | 257篇 |
2012年 | 330篇 |
2011年 | 282篇 |
2010年 | 161篇 |
2009年 | 140篇 |
2008年 | 178篇 |
2007年 | 128篇 |
2006年 | 121篇 |
2005年 | 99篇 |
2004年 | 78篇 |
2003年 | 92篇 |
2002年 | 79篇 |
2001年 | 40篇 |
2000年 | 56篇 |
1999年 | 60篇 |
1998年 | 34篇 |
1997年 | 30篇 |
1996年 | 23篇 |
1995年 | 30篇 |
1994年 | 26篇 |
1993年 | 22篇 |
1992年 | 32篇 |
1991年 | 24篇 |
1990年 | 23篇 |
1989年 | 19篇 |
1988年 | 15篇 |
1987年 | 14篇 |
1986年 | 9篇 |
1985年 | 9篇 |
1984年 | 7篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1976年 | 3篇 |
1973年 | 2篇 |
1969年 | 3篇 |
1966年 | 2篇 |
1951年 | 2篇 |
排序方式: 共有3935条查询结果,搜索用时 15 毫秒
81.
Xiao-Yu Ni Chang-Wang Pan B. Gangadhara Prusty 《Computer methods in biomechanics and biomedical engineering》2013,16(10):1117-1125
This paper discusses various issues relating to the mechanical properties of a braided non-vascular stent made of a Ni–Ti alloy. The design of the stent is a major factor which determines its reliability after implantation into a stenosed non-vascular cavity. This paper presents the effect of the main structural parameters on the mechanical properties of braided stents. A parametric analysis of a commercial stent model is developed using the commercial finite element code ANSYS. As a consequence of the analytical results that the pitch of wire has a greater effect than other structural parameters, a new design of a variable pitch stent is presented to improve mechanical properties of these braided stents. The effect of structural parameters on mechanical properties is compared for both stent models: constant and variable pitches. When the pitches of the left and right quarters of the stent are 50% larger and 100% larger than that of the central portion, respectively, the radial stiffness in the central portion increases by 10% and 38.8%, while the radial stiffness at the end portions decreases by 128% and 164.7%, the axial elongation by 25.6% and 56.6% and the bending deflection by 3.96% and 10.15%. It has been demonstrated by finite element analysis that the variable pitch stent can better meet the clinical requirements. 相似文献
82.
In this paper, the melting of ice 1h is studied using molecular dynamics (MD). Common potential functions employed in the MD simulations include SPC/E, TIP4P, TIP5P, TIP4/ice and TIP5P/E. We first conducted melting of ice bulks and then studied the melting speed of the ice/water interface during ice melting. It is found that various potentials result in similar ice-melting phenomena. The result is compared with the analytical solution for phase change problem. We also studied size effects and temperature gradient effects on ice melting. 相似文献
83.
84.
Pei-Ju Liu Yao-Shen Chen Hsi-Hsu Lin Wei-Feng Ni Tsung-Han Hsieh Hsu-Tzu Chen Ya-Lei Chen 《PLoS neglected tropical diseases》2013,7(8)
Background
Approximately 3–5% of patients with melioidosis manifest CNS symptoms; however, the clinical data regarding neurological melioidosis are limited.Methods and Findings
We established a mouse model of melioidosis with meningitis characterized by neutrophil infiltration into the meninges histologically and B. pseudomallei in the cerebrospinal fluid (CSF) by bacteriological culturing methods. As the disease progresses, the bacteria successively colonize the spleen, liver, bone marrow (BM) and brain and invade splenic and BM cells by days 2 and 6 post-infection, respectively. The predominant cell types intracellularly infected with B. pseudomallei were splenic and BM CD11b+ populations. The CD11b+Ly6Chigh inflamed monocytes, CD11b+Ly6Clow resident monocytes, CD11b+Ly6G+ neutrophils, CD11b+F4/80+ macrophages and CD11b+CD19+ B cells were expanded in the spleen and BM during the progression of melioidosis. After adoptive transfer of CD11b populations harboring B. pseudomallei, the infected CD11b+ cells induced bacterial colonization in the brain, whereas CD11b− cells only partially induced colonization; extracellular (free) B. pseudomallei were unable to colonize the brain. CD62L (selectin) was absent on splenic CD11b+ cells on day 4 but was expressed on day 10 post-infection. Adoptive transfer of CD11b+ cells expressing CD62L (harvested on day 10 post-infection) resulted in meningitis in the recipients, but transfer of CD11b+ CD62L-negative cells did not.Conclusions/Significance
We suggest that B. pseudomallei-infected CD11b+ selectin-expressing cells act as a Trojan horse and are able to transmigrate across endothelial cells, resulting in melioidosis with meningitis. 相似文献85.
Background
Cataract is the leading cause of blindness worldwide. Many observational studies assessed the relationship between postmenopausal hormone replacement therapy (HRT) and risk of cataract development, but the reported results were controversial. The aim of present meta-analysis was to evaluate the association of postmenopausal hormone replacement therapy with risk of cataract development.Methods
The eligible observational studies, including cross-sectional, case–control and cohort studies, were identified by searching PubMed and Embase during March of 2013. Either a fixed- or a random-effects model was used to calculate the pooled odds ratio (OR) with its 95% confidence interval (95%CI). Subgroup analysis on cataract types was performed.Results
A total of four cohort and five case-control or cross-sectional studies were finally included into this meta-analysis. Overall, a significant decreased risk of developing any type of cataract was found in ever HRT group as compared with non-HRT group among cohort studies (OR 0.83; 95%CI: 0.71,0.97) and case-control or cross-sectional studies (OR 0.74; 95%CI: 0.59,0.93). Subgroup analysis on cataract types determined that the significantly decreased risk of nuclear cataract in current HRT group (OR 0.72; 95%CI: 0.61,0.85) and also a critically reduced risk of nuclear cataract in ever HRT group (OR 0.80; 95% CI: 0.64,1.01) were found among case-control or cross-sectional studies, as compared with non-HRT group. No association of HRT with risk of cortical and posterior subcapsular cataract was observed.Conclusions
The results of present meta-analysis indicate that postmenopausal hormone use may play a protective role in cataract development. 相似文献86.
The stability and shapes of domains with different bending rigidities in lipid membranes are investigated. These domains can
be formed from the inclusion of an impurity in a lipid membrane or from the phase separation within the membrane. We show
that, for weak line tensions, surface tensions and finite spontaneous curvatures, an equilibrium phase of protruding circular
domains or striped domains may be obtained. We also predict a possible phase transition between the investigated morphologies. 相似文献
87.
Yike Yuan Yuwei Zhao Shengchang Xin Ni Wu Jiaolin Wen Song Li Lijuan Chen Yuquan Wei Hanshuo Yang Shuo Lin 《PloS one》2013,8(4)
The Hedgehog (Hh) pathway inhibitors have shown great promise in cancer therapeutics. SANT75, a novel compound we previously designed to specially inhibit the Smoothened (SMO) protein in the Hh pathway, has greater inhibitory potency than many of commonly used Hh inhibitors. However, preclinical studies of SANT75 revealed water insolubility and acute toxicity. To overcome these limitations, we developed a liposomal formulation of SANT75 and investigated its antitumor efficacy in vitro and in vivo. We encapsulated SANT75 into PEGylated liposome and the mean particle size distribution and zeta-potential (ZP) of liposomes were optimized. Using the Shh-light2 cell and Gli-GFP or Flk-GFP transgenic reporter zebrafish, we confirmed that liposome-encapsulated SANT75 inhibited Hh activity with similar potency as the original SANT75. SANT75 encapsulated into liposome exerted strong tumor growth-inhibiting effects in vitro and in vivo. In addition, the liposomal SANT75 therapy efficiently improved the survival time of tumor-bearing mice without obvious systemic toxicity. The pathological morphology and immunohistochemistry staining revealed that liposomal SANT75 induced tumor cell apoptosis, inhibited tumor angiogenesis as assessed by CD31 and down-regulated the expression of Hh target protein Gli-1 in tumor tissues. Our findings suggest that liposomal formulated SANT75 has improved solubility and bioavailability and should be further developed as a drug candidate for treating tumors with abnormally high Hh activity. 相似文献
88.
Louis Laviolette Marie-Cécile Niérat Anna L. Hudson Mathieu Raux étienne Allard Thomas Similowski 《PloS one》2013,8(4)
Introduction
In humans, cortical mechanisms can interfere with autonomic breathing. Respiratory-related activation of the supplementary motor area (SMA) has been documented during voluntary breathing and in response to inspiratory constraints. The SMA could therefore participate in the increased resting state of the respiratory motor system during wake (i.e. "wakefulness drive to breathe").Methods
The SMA was conditioned by continuous theta burst magnetic stimulation (cTBS, inhibitory) and 5 Hz conventional rTMS (5 Hz, excitatory). The ensuing effects were described in terms of the diaphragm motor evoked response (DiMEPs) to single-pulse transcranial magnetic stimulation over the motor cortex. DiMEPs were recorded at baseline, and at 3 time-points ("post1", "post2", "post3") up to 15 minutes following conditioning of the SMA.Results
cTBS reduced the amplitude of DiMEPs from 327.5±159.8 µV at baseline to 243.3±118.7 µV, 217.8±102.9 µV and 240.6±123.9 µV at post 1, post 2 and post 3, respectively (F = 6.341, p = 0.002). 5 Hz conditioning increased the amplitude of DiMEPs from 184.7±96.5 µV at baseline to 270.7±135.4 µV at post 3 (F = 4.844, p = 0.009).Conclusions
The corticospinal pathway to the diaphragm can be modulated in both directions by conditioning the SMA. This suggests that the baseline respiratory activity of the SMA represents an equipoise from which it is possible to move in either direction. The resting corticofugal outflow from the SMA to phrenic motoneurones that this study evidences could putatively contribute to the wakefulness drive to breathe. 相似文献89.
Five truncation mutants of chloroplast ATP synthase gamma subunit from spinach (Spinacia oleracea) lacking 8, 12, 16, 20 or 60 N-terminal amino acids were generated by PCR by a mutagenesis method. The recombinant gamma genes were overexpressed in Escherichia coli and assembled with alphabeta subunits into a native complex. The wild-type (WT) alphabetagamma assembly i.e. alphabetagammaWT exhibited high (Mg2+)-dependent and (Ca2+)-dependent ATP hydrolytic activity. Deletions of eight residues of the gamma subunit N-terminus caused a decrease in rates of ATP hydrolysis to 30% of that of the alphabetaWT assembly. Furthermore, only approximately 6% of ATP hydrolytic activity was retained with the sequential deletions of gamma subunit up to 20 residues compared with the activity of the alphabetaWT assembly. The inhibitory effect of the epsilon subunit on ATP hydrolysis of these alphabetagamma assemblies varied to a large extent. These observations indicate that the N-terminus of the gamma subunit is very important, together with other regions of the gamma subunit, in stabilization of the enzyme complex or during cooperative catalysis. In addition, the in vitro binding assay showed that the gamma subunit N-terminus is not a crucial region in binding of the epsilon subunit. 相似文献
90.
Li Ni‐Komatsu Jennifer K. Leung Darren Williams Jaeki Min Sonya M. Khersonsky Young‐Tae Chang Seth J. Orlow 《Pigment cell & melanoma research》2005,18(6):447-453
As most of the available depigmenting agents exhibit only modest activity and some exhibit toxicities that lead to adverse side effects after long‐term usage, there remains a need for novel depigmenting agents. Chemical genetic screening was performed on cultured melanocytes to identify novel depigmenting compounds. By screening a tagged‐triazine library, we identified four compounds, TGH11, TGD10, TGD39 and TGJ29, as potent pigmentation inhibitors with IC50 values in the range of 10 μM. These newly identified depigmenting compounds were found to function as reversible inhibitors of tyrosinase, the key enzyme involved in melanin synthesis. Tyrosinase was further confirmed as the cellular target of these compounds by affinity chromatography. Kinetic data suggest that all four compounds act as competitive inhibitors of tyrosinase, most likely competing with l ‐3,4‐dihydroxyphenylalanine (l ‐DOPA) for binding to the DOPA‐binding site of the enzyme. No effect on levels of tyrosinase protein, processing or trafficking was observed upon treatment of melanocytes with these compounds. Cytotoxicity was not observed with these compounds at concentrations up to 20 μM. Our data suggest that TGH11, TGD10, TGD39 and TGJ29 are novel potent tyrosinase inhibitors with potential beneficial effects in the treatment of cutaneous hyperpigmentation. 相似文献