全文获取类型
收费全文 | 2390篇 |
免费 | 153篇 |
国内免费 | 3篇 |
专业分类
2546篇 |
出版年
2024年 | 2篇 |
2023年 | 17篇 |
2022年 | 43篇 |
2021年 | 107篇 |
2020年 | 35篇 |
2019年 | 46篇 |
2018年 | 83篇 |
2017年 | 60篇 |
2016年 | 93篇 |
2015年 | 107篇 |
2014年 | 158篇 |
2013年 | 185篇 |
2012年 | 216篇 |
2011年 | 252篇 |
2010年 | 139篇 |
2009年 | 136篇 |
2008年 | 148篇 |
2007年 | 123篇 |
2006年 | 113篇 |
2005年 | 83篇 |
2004年 | 93篇 |
2003年 | 65篇 |
2002年 | 63篇 |
2001年 | 18篇 |
2000年 | 18篇 |
1999年 | 12篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1994年 | 6篇 |
1993年 | 9篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 9篇 |
1987年 | 10篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1983年 | 6篇 |
1982年 | 2篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1976年 | 3篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1970年 | 3篇 |
1964年 | 1篇 |
排序方式: 共有2546条查询结果,搜索用时 15 毫秒
111.
Pandey AV Babbarwal VK Okoyeh JN Joshi RM Puri SK Singh RL Chauhan VS 《Biochemical and biophysical research communications》2003,308(4):736-743
Major blood stage antimalarial drugs like chloroquine and artemisinin target the heme detoxification process of the malaria parasite. Hemozoin formation reactions in vitro using the Plasmodium falciparum histidine-rich protein-2 (Pfhrp-2), lipids, and auto-catalysis are slow and could not explain the speed of detoxification needed for parasite survival. Here, we show that malarial hemozoin formation is a coordinated two component process involving both lipids and histidine-rich proteins. Hemozoin formation efficiency in vitro is 1-2% with Pfhrp-2 and 0.25-0.5% with lipids. We added lipids after 9h in a 12h Pfhrp-2 mediated reaction that resulted in sixfold increase in hemozoin formation. However, a lipid mediated reaction in which Pfhrp-2 was added after 9h produced only twofold increase in hemozoin production compared to the reaction with Pfhrp-2 alone. Synthetic peptides corresponding to the Pfhrp-2 heme binding sequences, based on repeats of AHHAAD, neither alone nor in combination with lipids were able to generate hemozoin in vitro. These results indicate that hemozoin formation in malaria parasite involves both the lipids and the scaffolding proteins. Histidine-rich proteins might facilitate hemozoin formation by binding with a large number of heme molecules, and facilitating the dimer formation involving iron-carboxylate bond between two heme molecules, and lipids may then subsequently assist the mechanism of long chain formation, held together by hydrogen bonds or through extensive networking of hydrogen bonds. 相似文献
112.
Amit?K?Trivedi Sangeeta?Rani Vinod?KumarEmail author 《Reproductive biology and endocrinology : RB&E》2004,2(1):79
Little is known about how hormones interact in the photoperiodic induction of seasonal responses in birds. In this study,
two experiments determined if the treatment with melatonin altered inhibitory effects of prolactin on photoperiodic induction
of seasonal responses in the Palearctic-Indian migratory male redheaded bunting Emberiza bruniceps. Each experiment employed three groups (N = 6–7 each) of photosensitive birds that were held under 8 hours light: 16 hours
darkness (8L:16D) since early March. In the experiment 1, beginning in mid June 2001, birds were exposed to natural day lengths
(NDL) at 27 degree North (day length = ca.13.8 h, sunrise to sunset) for 23 days. In the experiment 2, beginning in early
April 2002, birds were exposed to 14L:10D for 22 days. Beginning on day 4 of NDL or day 1 of 14L:10D, they received 10 (experiment
1) or 13 (experiment 2) daily injections of both melatonin and prolactin (group 1) or prolactin alone (group 2) at a dose
of 20 microgram per bird per day in 200 microliter of vehicle. Controls (group 3) received similar volume of vehicle. Thereafter,
birds were left uninjected for the next 10 (experiment 1) or 9 days (experiment 2). All injections except those of melatonin
were made at the zeitgeber time 10 (ZT 0 = time of sunrise, experiment 1; time of lights on, experiment 2); melatonin was
injected at ZT 9.5 and thus 0.5 h before prolactin. Observations were recorded on changes in body mass, testicular growth
and feather regeneration. 相似文献
113.
Won Jun Choi Hyuk Woo Lee Hea Ok Kim Moshe Chinn Zhan-Guo Gao Amit Patel Kenneth A. Jacobson Hyung Ryong Moon Young Hoon Jung Lak Shin Jeong 《Bioorganic & medicinal chemistry》2009,17(23):8003-8011
On the basis of a bioisosteric rationale, 4′-thionucleoside analogues of IB-MECA (N6-(3-Iodo-benzyl)-9-(5′-methylaminocarbonyl-β-d-ribofuranosyl)adenine), which is a potent and selective A3 adenosine receptor (AR) agonist, were synthesized from d-gulonic acid γ-lactone. The 4′-thio analogue (5h) of IB-MECA showed extremely high binding affinity (Ki = 0.25 nM) at the human A3AR and was more potent than IB-MECA (Ki = 1.4 nM). Bulky substituents at the 5′-uronamide position, such as cyclohexyl and 2-methylbenzyl, in this series of 2-H nucleoside derivatives were tolerated in A3AR binding, although small alkyl analogues were more potent. 相似文献
114.
Chinnapaka Somaiah Atul Kumar Darilang Mawrie Amit Sharma Suraj Dasharath Patil Jina Bhattacharyya Rajaram Swaminathan Bithiah Grace Jaganathan 《PloS one》2015,10(12)
Mesenchymal stem cells (MSC) can differentiate into several cell types and are desirable candidates for cell therapy and tissue engineering. However, due to poor cell survival, proliferation and differentiation in the patient, the therapy outcomes have not been satisfactory. Although several studies have been done to understand the conditions that promote proliferation, differentiation and migration of MSC in vitro and in vivo, still there is no clear understanding on the effect of non-cellular bio molecules. Of the many factors that influence the cell behavior, the immediate cell microenvironment plays a major role. In this context, we studied the effect of extracellular matrix (ECM) proteins in controlling cell survival, proliferation, migration and directed MSC differentiation. We found that collagen promoted cell proliferation, cell survival under stress and promoted high cell adhesion to the cell culture surface. Increased osteogenic differentiation accompanied by high active RHOA (Ras homology gene family member A) levels was exhibited by MSC cultured on collagen. In conclusion, our study shows that collagen will be a suitable matrix for large scale production of MSC with high survival rate and to obtain high osteogenic differentiation for therapy. 相似文献
115.
Mitomycin C (MC), an antitumor antibiotic, alkylated Z-DNAs such as poly(dG-dC)/Co(NH3)3+(6), poly(dG-m5dC)/Mg2+ and brominated poly(dG-dC) upon reductive activation. Computer-generated energy-minimized molecular models indicated that monofunctional alkylation of Z-DNA at the N2-position of guanine by MC did not distort Z-DNA geometry, but bifunctional alkylation, leading to interstrand crosslinks between two N2-positions of guanine was sterically unfavorable. The above three Z-DNA's were exposed both to monofunctionally and bifunctionally activated MC in separate experiments and the resulting covalent MC-polynucleotide complexes were examined for conformation and for covalent MC-adducts, by circular dichroism (CD) spectroscopy and HPLC analysis of nuclease digests, respectively. Monofunctionally activated MC alkylated all three polynucleotides in their Z-forms, resulting in the same monofunctional N2-guanine adduct as that known to be formed with B-DNA. Upon bifunctional activation of MC, poly(dG-dC/Co(NH3)3+(6) reverted to the B-form and bifunctional (cross-link) adducts were detected, identical again with those formed with B-DNA. Poly(dG-m5dC), however, remained in the Z-form after the alkylation and only a monofunctional adduct could be detected. It was concluded that Z-DNA is subject to monofunctional alkylation by MC but cannot be cross-linked. The latter process occurs only when the Z-DNA is labile enough [as is in the case of poly(dG-dC)] to have some B-form in equilibrium at the site of the first formed monolinked adduct; the cross-linking then occurs at such local B-sites, pulling the overall B in equilibrium Z equilibrium irreversibly to the left. These results are in accord with the predictions from the above modeling. The irreversible "lock" by the MC cross-link on B-DNA may be exploited for probing Z-DNA intermediacy in various DNA functions. 相似文献
116.
Vincent T Saikali P Cayrol R Roth AD Bar-Or A Prat A Antel JP 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(8):5730-5737
Autoantibody neuromyelitis optica-IgG (NMO-IgG) recognizing aquaporin-4 (AQP4) is implicated as playing a central role in the physiopathology of NMO. The aim of this in vitro-based study was to characterize functional consequences of interaction between NMO-IgG and cells of the neurovascular unit (astrocytes and brain endothelium) that would provide insight into recognized features of NMO, namely altered blood-brain barrier (BBB) permeability and granulocyte recruitment. We used sera from NMO and longitudinally extensive transverse myelitis cases shown to bind in a characteristic perivascular pattern to primate cerebellar slices. Using flow cytometry, we found that sera from NMO-IgG-positive patients reacted with CNS-derived human fetal astrocytes, whereas sera from multiple sclerosis patients did not. We demonstrated that NMO-IgG binding to astrocytes alters aquaporin-4 polarized expression and increases permeability of a human BBB endothelium/astrocyte barrier. We further demonstrated that NMO-IgG binding to human fetal astrocytes can result in NK cell degranulation, astrocyte killing by Ab-dependent cellular cytotoxicity and complement-dependent granulocyte attraction through the BBB model. Our study highlights important functional roles for NMO-IgG that could account for pathological lesions and BBB dysfunction observed in NMO. 相似文献
117.
118.
Gundeep Kaur Supreet Singh Harpreet Singh Mrinalini Chawla Tanima Dutta Harsimran Kaur Kyle Bender W. A. Snedden Sanjay Kapoor Ashwani Pareek Prabhjeet Singh 《PloS one》2015,10(8)
Cyclophilins, which bind to immunosuppressant cyclosporin A (CsA), are ubiquitous proteins and constitute a multigene family in higher organisms. Several members of this family are reported to catalyze cis-trans isomerisation of the peptidyl-prolyl bond, which is a rate limiting step in protein folding. The physiological role of these proteins in plants, with few exceptions, is still a matter of speculation. Although Arabidopsis genome is predicted to contain 35 cyclophilin genes, biochemical characterization, imperative for understanding their cellular function(s), has been carried only for few of the members. The present study reports the biochemical characterization of an Arabidopsis cyclophilin, AtCyp19-3, which demonstrated that this protein is enzymatically active and possesses peptidyl-prolyl cis-trans isomerase (PPIase) activity that is specifically inhibited by CsA with an inhibition constant (Ki) of 18.75 nM. The PPIase activity of AtCyp19-3 was also sensitive to Cu2+, which covalently reacts with the sulfhydryl groups, implying redox regulation. Further, using calmodulin (CaM) gel overlay assays it was demonstrated that in vitro interaction of AtCyp19-3 with CaM is Ca2+-dependent, and CaM-binding domain is localized to 35–70 amino acid residues in the N-terminus. Bimolecular fluorescence complementation assays showed that AtCyp19-3 interacts with CaM in vivo also, thus, validating the in vitro observations. However, the PPIase activity of the Arabidopsis cyclophilin was not affected by CaM. The implications of these findings are discussed in the context of Ca2+ signaling and cyclophilin activity in Arabidopsis. 相似文献
119.
120.