全文获取类型
收费全文 | 1714篇 |
免费 | 126篇 |
专业分类
1840篇 |
出版年
2022年 | 13篇 |
2021年 | 21篇 |
2020年 | 11篇 |
2019年 | 11篇 |
2018年 | 14篇 |
2017年 | 12篇 |
2016年 | 29篇 |
2015年 | 42篇 |
2014年 | 65篇 |
2013年 | 82篇 |
2012年 | 89篇 |
2011年 | 103篇 |
2010年 | 51篇 |
2009年 | 59篇 |
2008年 | 100篇 |
2007年 | 119篇 |
2006年 | 108篇 |
2005年 | 97篇 |
2004年 | 103篇 |
2003年 | 91篇 |
2002年 | 92篇 |
2001年 | 54篇 |
2000年 | 44篇 |
1999年 | 59篇 |
1998年 | 23篇 |
1997年 | 19篇 |
1996年 | 21篇 |
1995年 | 23篇 |
1994年 | 19篇 |
1993年 | 7篇 |
1992年 | 26篇 |
1991年 | 26篇 |
1990年 | 14篇 |
1989年 | 18篇 |
1988年 | 14篇 |
1987年 | 16篇 |
1986年 | 15篇 |
1985年 | 22篇 |
1984年 | 16篇 |
1983年 | 10篇 |
1981年 | 5篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1976年 | 5篇 |
1974年 | 4篇 |
1970年 | 4篇 |
1969年 | 4篇 |
1941年 | 4篇 |
1935年 | 3篇 |
1933年 | 4篇 |
排序方式: 共有1840条查询结果,搜索用时 0 毫秒
71.
Mads K Dalsgaard Stefanos Volianitis Chie C Yoshiga Ellen A Dawson Niels H Secher 《Journal of applied physiology》2004,97(5):1733-1739
When continuation of exercise calls for a "will," the cerebral metabolic ratio of O2 to (glucose + lactate) decreases, with the largest reduction (30-50%) at exhaustion. Because a larger effort is required to exercise with the arms than with the legs, we tested the hypothesis that the reduction in the cerebral metabolic ratio would become more pronounced during arm cranking than during leg exercise. The cerebral arterial-venous differences for blood-gas variables, glucose, and lactate were evaluated in two groups of eight subjects during exhaustive arm cranking and leg exercise. During leg exercise, exhaustion was elicited after 25 +/- 6 (SE) min, and the cerebral metabolic ratio was reduced from 5.6 +/- 0.2 to 3.5 +/- 0.2 after 10 min and to 3.3 +/- 0.3 at exhaustion (P < 0.05). Arm cranking lasted for 35 +/- 4 min and likewise decreased the cerebral metabolic ratio after 10 min (from 6.7 +/- 0.4 to 5.0 +/- 0.3), but the nadir at exhaustion was only 4.7 +/- 0.4, i.e., higher than during leg exercise (P < 0.05). The results demonstrate that exercise decreases the cerebral metabolic ratio when a conscious effort is required, irrespective of the muscle groups engaged. However, the comparatively small reduction in the cerebral metabolic ratio during arm cranking suggests that it is influenced by the exercise paradigm. 相似文献
72.
Maki Seki Osamu Tsuruta Ryo Tatsumi Aki Soejima 《Bioorganic & medicinal chemistry letters》2013,23(14):4230-4234
A novel series of pyrrolidine derivatives as Na+ channel blockers was synthesized and evaluated for their inhibitory effects on neuronal Na+ channels. Structure–activity relationship (SAR) studies of a pyrrolidine analogue 2 led to the discovery of 5e as a potent Na+ channel blocker with a low inhibitory action against human ether-a-go-go-related gene (hERG) channels. Compound 5e showed remarkably neuroprotective activity in a rat transient middle cerebral artery occlusion (MCAO) model, suggesting that 5e would act as a neuroprotectant for ischemic stroke. 相似文献
73.
We have developed a new NIR fluorescent probe based on an ytterbium(III) (E)‐1‐(pyridin‐2‐yl‐diazenyl)naphthalen‐2‐ol (PAN) complex. This probe emits near‐infrared luminescence derived from the Yb ion through excitation of the PAN moiety with visible light (λex = 530 nm, λem = 975 nm). The results support the possible utility of the probe for in vivo fluorescence molecular imaging. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
74.
Identification of cold-inducible downstream genes of the Arabidopsis DREB1A/CBF3 transcriptional factor using two microarray systems 总被引:20,自引:0,他引:20
75.
Hohsaka T Muranaka N Komiyama C Matsui K Takaura S Abe R Murakami H Sisido M 《FEBS letters》2004,560(1-3):173-177
Novel non-natural amino acids carrying a dansyl fluorescent group were designed, synthesized, and incorporated into various positions of streptavidin by using a CGGG four-base codon in an Escherichia coli in vitro translation system. 2,6-Dansyl-aminophenylalanine (2,6-dnsAF) was found to be incorporated into the protein more efficiently than 1,5-dansyl-lysine, 2,6-dansyl-lysine, and 1,5-dansyl-aminophenylalanine. Fluorescence measurements indicate that the position-specific incorporation of the 2,6-dnsAF is a useful technique to probe protein structures. These results also indicate that well-designed non-natural amino acids carrying relatively large side chains can be accepted as substrates of the translation system. 相似文献
76.
Low-fidelity DNA synthesis by human DNA polymerase theta 总被引:1,自引:1,他引:1
Human DNA polymerase theta (pol θ or POLQ) is a proofreading-deficient family A enzyme implicated in translesion synthesis (TLS) and perhaps in somatic hypermutation (SHM) of immunoglobulin genes. These proposed functions and kinetic studies imply that pol θ may synthesize DNA with low fidelity. Here, we show that when copying undamaged DNA, pol θ generates single base errors at rates 10- to more than 100-fold higher than for other family A members. Pol θ adds single nucleotides to homopolymeric runs at particularly high rates, exceeding 1% in certain sequence contexts, and generates single base substitutions at an average rate of 2.4 × 10−3, comparable to inaccurate family Y human pol κ (5.8 × 10−3) also implicated in TLS. Like pol κ, pol θ is processive, implying that it may be tightly regulated to avoid deleterious mutagenesis. Pol θ also generates certain base substitutions at high rates within sequence contexts similar to those inferred to be copied by pol θ during SHM of immunoglobulin genes in mice. Thus, pol θ is an exception among family A polymerases, and its low fidelity is consistent with its proposed roles in TLS and SHM. 相似文献
77.
Takahashi K Yamaguchi S Shimoyama T Seki H Miyokawa K Katsuta H Tanaka T Yoshimoto K Ohno H Nagamatsu S Ishida H 《American journal of physiology. Endocrinology and metabolism》2008,294(5):E898-E909
Obese conditions increase the expression of adipocytokine monocyte chemoattractant protein-1 (MCP-1) in adipose tissue as well as MCP-1 plasma levels. To investigate the mechanism behind increased MCP-1, we used a model in which 3T3-L1 adipocytes were artificially hypertrophied by preloading with palmitate in vitro. As observed in obesity, under our model conditions, palmitate-preloaded cells showed significantly increased oxidative stress and increased MCP-1 expression relative to control cells. This increased MCP-1 expression was enhanced by adding exogenous tumor necrosis factor-alpha (TNF-alpha; 17.8-fold vs. control cells, P < 0.01) rather than interleukin-1beta (IL-1beta; 2.6-fold vs. control cells, P < 0.01). However, endogenous TNF-alpha and IL-1beta release was not affected in hypertrophied cells, suggesting that these endogenous cytokines do not mediate hypertrophy-induced increase in MCP-1. MCP-1 secretion from hypertrophied cells was significantly decreased by treatment with antioxidant N-acetyl-cysteine, JNK inhibitors SP600125 and JIP-1 peptide, and IkappaB phosphorylation inhibitors BAY 11-7085 and BMS-345541 (P < 0.01). MCP-1 secretion was not affected by peroxisome proliferator-activated receptor-gamma (PPARgamma) antagonists assayed. Adiponectin, another adipocytokine studied in parallel, also showed increased release in hypertrophy relative to control cells. But in contrast to MCP-1, adiponectin release was significantly suppressed by both exogenous TNF-alpha and IL-1beta as well as by PPARgamma antagonists bisphenol A diglycidyl ether and T0070907 (P < 0.01). JNK inhibitors and IkappaB phosphorylation inhibitors showed no significant effect on adiponectin. We conclude that adipocyte hypertrophy through palmitate loading causes oxidative stress, which in turn increases MCP-1 expression and secretion through JNK and IkappaB signaling. In contrast, the parallel increase in adiponectin expression appears to be related to the PPARgamma ligand properties of palmitate. 相似文献
78.
79.
Tochio N Umehara T Koshiba S Inoue M Yabuki T Aoki M Seki E Watanabe S Tomo Y Hanada M Ikari M Sato M Terada T Nagase T Ohara O Shirouzu M Tanaka A Kigawa T Yokoyama S 《Structure (London, England : 1993)》2006,14(3):457-468
SWIRM is an evolutionarily conserved domain involved in several chromatin-modifying complexes. Recently, the LSD1 protein, which bears a SWIRM domain, was found to be a demethylase for Lys4-methylated histone H3. Here, we report a solution structure of the SWIRM domain of human LSD1. It forms a compact fold composed of 6 alpha helices, in which a 20 amino acid long helix (alpha4) is surrounded by 5 other short helices. The SWIRM domain structure could be divided into the N-terminal part (alpha1-alpha3) and the C-terminal part (alpha4-alpha6), which are connected to each other by a salt bridge. While the N-terminal part forms a SWIRM-specific structure, the C-terminal part adopts a helix-turn-helix (HTH)-related fold. We discuss a model in which the SWIRM domain acts as an anchor site for a histone tail. 相似文献
80.
Jun Iwamoto Azusa Seki Tsuyoshi Takeda Yoshihiro Sato Harumoto Yamada James K Yeh 《Experimental Animals》2006,55(4):333-342
The purpose of the present study was to compare the therapeutic effects of risedronate (RIS) and alfacalcidol (ALF) on cancellous and cortical bone in ovariectomized osteopenic rats. Forty-two female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into six groups: the sham-operated control (Sham) group, and five ovariectomized groups: treated with vehicle, RIS (0.1, 1.0, or 2.5 mg/kg, p.o., daily), and ALF (0.5 microg/kg, p.o., daily). Treatment was started 6 weeks after surgery and continued for 6 weeks. Evaluation at 12 weeks after surgery revealed that ovariectomy (OVX) decreased the cancellous bone volume/total tissue volume (BV/TV) of the proximal tibial metaphysis as a result of an increase of the bone formation rate/bone surface (BFR/BS), BFR/BV, and eroded surface (ES/BS), while having no effect on the cortical area (Ct Ar) of the tibial diaphysis. OVX also decreased the maximum load of the femoral distal metaphysis, while having no effect on any mechanical property parameters of the femoral diaphysis. RIS (at all the doses) increased the BV/TV relative to the value in the OVX-Vehicle group, but the value was not restored to that observed in the Sham group. The effects of RIS (1.0 mg/kg and 2.5 mg/kg) were similar, and greater than those of RIS (0.1 mg/kg). ALF also increased the BV/TV relative to the OVX-Vehicle group, but the value was not restored to that observed in the Sham group, similar to the results of RIS (1.0 mg/kg and 2.5 mg/kg) treatment. The alterations of the structural parameters induced by RIS (at the doses) were attributable to suppression of the increase of ES/BS, BFR/BS, and BFR/BV. The alterations of the structural parameters induced by ALF were attributable to suppression of the increase of ES/BS and attenuation of the increase of BFR/BV, while the BFR/BS was maintained. ALF also increased the Ct Ar to beyond the value observed in the Sham group. RIS (at all the doses) had no effect on the mechanical properties of the femoral distal metaphysis, whereas ALF prevented the loss of the maximum load of the femoral distal metaphysis. Thus, the results of the present study show differential effects of RIS and ALF on cancellous and cortical bone in ovariectomized osteopenic rats. 相似文献