全文获取类型
收费全文 | 2245篇 |
免费 | 207篇 |
国内免费 | 4篇 |
专业分类
2456篇 |
出版年
2023年 | 11篇 |
2022年 | 27篇 |
2021年 | 33篇 |
2020年 | 17篇 |
2019年 | 23篇 |
2018年 | 28篇 |
2017年 | 16篇 |
2016年 | 47篇 |
2015年 | 88篇 |
2014年 | 113篇 |
2013年 | 95篇 |
2012年 | 169篇 |
2011年 | 134篇 |
2010年 | 91篇 |
2009年 | 71篇 |
2008年 | 130篇 |
2007年 | 119篇 |
2006年 | 123篇 |
2005年 | 104篇 |
2004年 | 90篇 |
2003年 | 92篇 |
2002年 | 77篇 |
2001年 | 66篇 |
2000年 | 61篇 |
1999年 | 33篇 |
1998年 | 19篇 |
1997年 | 19篇 |
1996年 | 19篇 |
1995年 | 14篇 |
1994年 | 22篇 |
1993年 | 12篇 |
1992年 | 27篇 |
1991年 | 32篇 |
1990年 | 23篇 |
1989年 | 34篇 |
1988年 | 34篇 |
1987年 | 31篇 |
1986年 | 33篇 |
1985年 | 32篇 |
1984年 | 19篇 |
1983年 | 23篇 |
1982年 | 19篇 |
1981年 | 16篇 |
1980年 | 11篇 |
1979年 | 22篇 |
1978年 | 14篇 |
1977年 | 24篇 |
1976年 | 14篇 |
1974年 | 12篇 |
1973年 | 17篇 |
排序方式: 共有2456条查询结果,搜索用时 15 毫秒
81.
Bovine or rat brain adenylate cyclase (EC 4.6.1.1) solubilized by Lubrol-PX, a nonionic detergent, requires a Ca2+-binding protein activator for full activity (Cheung et al., 1975, Biochem. Biophys. Res. Commun.66, 1055–1062). We now show that particulate rat brain adenylate cyclase also required the activator for maximum activity. A brain particulate fraction was extracted with a hypertonic NaCl solution containing [ethyl-enebis(oxyethylenenitrilo)] tetraacetic acid. This procedure removed preferentially the activator, making adenylate Cyclase activator deficient and, consequently, dependent on an exogenous activator for maximum activity. The activator increased the V of adenylate cyclase without affecting its apparent Km for ATP. In the presence of the activator, the enzyme was more stable against thermal inactivation, suggesting that the activator probably induced a conformational change to the enzyme. F? and 5′-guanylylimidodi-phosphate [GMP-p(NH)p] greatly stimulated brain adenylate cyclase. Adenylate cyclase activity obtained in the presence of the activator and F? was comparable to the summed activities of the two agents assayed separately, indicating that their effects were additive. Similarly, the effects of the activator and GMP-p(NH)p were additive. These results suggest that the action of the activator is independent of the other two ligands. Since the activator is present in excess over adenylate cyclase, the cellular flux of Ca2+ is believed to be important in modulating the enzyme activity. The role of the Ca2+/ activator is discussed with respect to cyclic AMP metabolism in brain. 相似文献
82.
B. Akbar John B. R. Nelson Hassan I. Sheikh S. G. Cheung Yusli Wardiatno Bisnu Prasad Dash Keiji Tsuchiya Yumiko Iwasaki Siddhartha Pati 《Biodiversity and Conservation》2018,27(14):3573-3598
Horseshoe crabs are the only extant xiphosurans and are believed to be morphologically unchanged for more than 200 million years. Of the four extant species namely, Limulus polyphemus, Tachypleus tridentatus, Tapinauchenius gigas and Carcinoscorpius rotundicauda, the latter three are found in Asian waters. Recent evidences showed that Asian horseshoe crabs are facing serious threats such as degradation of their spawning grounds and habitat, environmental pollution, overexploitation as a culinary delicacy and biomedical bleeding practices. Baseline data on the distribution and existing population of the wild horseshoe crabs remain poorly known in several Asian regions. Several studies have clearly revealed that pressure due to over-fishing of wild stock has increased tremendously in the last decade. Due to an increase in demand for Tachypleus Amebocyte Lysate (TAL) analogous to Limulus Amebocyte Lysate (LAL) in the United States, there is an urgent need to comprehensively address their fishing and conservation measures in the Asian region. This review addresses the overall studies on three species of Asian horseshoe crabs in relation to their fishing practices, local exploitation of their wild stock either for human consumption (or) by biomedical industries. The authors have structured the discussion on an international scale to address the existing problems in fishing and conservation of horseshoe crabs. Since no specific regulatory force or legislative protection act or a policy to preserve their natural stock are available to this date, this paper strongly recommends representative countries to include horseshoe crabs under their wildlife protection act to avoid further unsustainable exploitation of their wild populations. 相似文献
83.
Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, particularly in southern regions of China. EBV infection is closely associated with NPC and has long been postulated to play an etiological role in the development of NPC. However, the role of EBV in malignant transformation of nasopharyngeal epithelial cells remains enigmatic. The current hypothesis of NPC development is that premalignant nasopharyngeal epithelial cells harboring genetic alterations support EBV infection and expression of EBV genes induces further genomic instability to facilitate the development of NPC. The latent membrane protein 1 (LMP1) is a well-documented EBV-encoded oncogene. The involvement of LMP1 in human epithelial malignancies has been implicated, but the mechanisms of oncogenic actions of LMP1, particularly in nasopharyngeal cells, are unclear. Here we observed that LMP1 expression in nasopharyngeal epithelial cells impaired G2 checkpoint, leading to formation of unrepaired chromatid breaks in metaphases after γ-ray irradiation. We further found that defective Chk1 activation was involved in the induction of G2 checkpoint defect in LMP1-expressing nasopharyngeal epithelial cells. Impairment of G2 checkpoint could result in loss of the acentrically broken chromatids and propagation of broken centric chromatids in daughter cells exiting mitosis, which facilitates chromosome instability. Our findings suggest that LMP1 expression facilitates genomic instability in cells under genotoxic stress. Elucidation of the mechanisms involved in LMP1-induced genomic instability in nasopharyngeal epithelial cells will shed lights on the understanding of role of EBV infection in NPC development. 相似文献
84.
85.
86.
p33(ING1) enhances UVB-induced apoptosis in melanoma cells 总被引:14,自引:0,他引:14
The biological functions of the tumor suppressor ING1 have been studied extensively in the past few years since it was cloned. It shares many biological functions with p53 and has been reported to mediate growth arrest, senescence, apoptosis, anchorage-dependent growth, chemosensitivity, and DNA repair. Some of these functions, such as cell cycle arrest and apoptosis, have been shown to be dependent on the activity of both ING1 and p53 proteins. Two recent reports by Scott and colleagues demonstrate that p33(ING1) (one of the ING1 isoforms) translocates to the nucleus and binds to PCNA upon UV irradiation. Here we report that p33(ING1) mediates UV-induced cell death in melanoma cells. We found that overexpression of p33(ING1) increased while the introduction of an antisense p33(ING1) plasmid reduced the apoptosis rate in melanoma cells after UVB irradiation. We also demonstrated that enhancement of UV-induced apoptosis by p33(ING1) required the presence of p53. Moreover, we found that p33(ING1) enhanced the expression of endogenous Bax and altered the mitochondrial membrane potential. Taken together, these observations strongly suggest that p33(ING1) cooperates with p53 in UVB-induced apoptosis via the mitochondrial cell death pathway in melanoma cells. 相似文献
87.
Yuen‐Ting Cheung Natalie Qishan Zhang Clara Hiu‐Ling Hung Cora Sau‐Wan Lai Man‐Shan Yu Kwok‐Fai So Raymond Chuen‐Chung Chang 《Journal of cellular and molecular medicine》2011,15(2):244-257
Alzheimer's disease (AD) is an aging‐related progressive neurodegenerative disorder. Previous studies suggested that various soluble Aβ species are neurotoxic and able to activate apoptosis and autophagy, the type I and type II programmed cell death, respectively. However, the sequential and functional relationships between these two cellular events remain elusive. Here we report that low molecular weight Aβ triggered cleavage of caspase 3 and poly (ADP‐ribose) polymerase to cause neuronal apoptosis in rat cortical neurons. On the other hand, Aβ activated autophagy by inducing autophagic vesicle formation and autophagy related gene 12 (ATG12), and up‐regulated the lysoso‐mal machinery for the degradation of autophagosomes. Moreover, we demonstrated that activation of autophagy by Aβ preceded that of apoptosis, with death associated protein kinase phosphorylation as the potential molecular link. More importantly, under Aβ toxicity, neurons exhibiting high level of autophagosome formation were absent of apoptotic features, and inhibition of autophagy by 3‐methylade‐nine advanced neuronal apoptosis, suggesting that autophagy can protect neurons from Aβ‐induced apoptosis. 相似文献
88.
Benjamin Chun-Kit Tong Aston Jiaxi Wu Min Li King-Ho Cheung 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2018,1865(11):1745-1760
Alzheimer's disease (AD) is the most common type of dementia and is characterized by the accumulation of amyloid (Aβ) plaques and neurofibrillary tangles in the brain. Much attention has been given to develop AD treatments based on the amyloid cascade hypothesis; however, none of these drugs had good efficacy at improving cognitive functions in AD patients suggesting that Aβ might not be the disease origin. Thus, there are urgent needs for the development of new therapies that target on the proximal cause of AD. Cellular calcium (Ca2+) signals regulate important facets of neuronal physiology. An increasing body of evidence suggests that age-related dysregulation of neuronal Ca2+ homeostasis may play a proximal role in the pathogenesis of AD as disrupted Ca2+ could induce synaptic deficits and promote the accumulation of Aβ plaques and neurofibrillary tangles. Given that Ca2+ disruption is ubiquitously involved in all AD pathologies, it is likely that using chemical agents or small molecules specific to Ca2+ channels or handling proteins on the plasma membrane and membranes of intracellular organelles to correct neuronal Ca2+ dysregulation could open up a new approach to AD prevention and treatment. This review summarizes current knowledge on the molecular mechanisms linking Ca2+ dysregulation with AD pathologies and discusses the possibility of correcting neuronal Ca2+ disruption as a therapeutic approach for AD. 相似文献
89.
Little information is available on the interaction between lymphocytes and fibronectin (fn). To gain a better understanding on this issue we examined the adhesion of 12 lymphoid cell lines, each exhibiting different phenotypic characteristics, to fn-coated substratum. Of the cell lines tested, five that adhered to fn possessed B-cell characteristics, while neither the T-cell lines nor the pre-B-cell line adhered. The physiology and biochemistry of adhesion of a B-cell line, MOPC 315, were examined in detail. Our results indicated that (1) the adhesion was a specific and time-dependent process, (2) the adhesion was temperature-dependent and inhibited by metabolic inhibitors, such as KCN and 2-deoxyglucose, (3) the presence of cycloheximide and pretreatment of cells with trypsin inhibited adhesion, (4) a 140-kDa surface protein was immunoprecipitated by anti-fn receptor antibodies, (5) the presence of divalent cations was essential for adhesion, (6) the presence of colchicine had no effect on adhesion, while cytochalasin B partially inhibited adhesion, and (7) the treatment of cells by both phorbol 12-myristate 13-acetate and calcium ionophore A23187 enhanced adhesion. In this study, we have established the interaction between lymphoid cell lines and fn. Such an interaction might play an important role in the behavior of lymphocytes in tissues. 相似文献
90.