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71.
72.
This study examined the important relationship between cystathionine γ-lyase (CSE) functionality and cysteine supply for normal growth and life span. Mice with a targeted deletion of the CSE gene (CSE-KO) were fed a cysteine-limited diet and their growth and survival patterns as well as levels of cysteine, homocysteine, glutathione, and hydrogen sulfide (H2S) were measured. CSE-KO mice fed a cysteine-limited diet exhibited growth retardation; decreased levels of cysteine, glutathione, and H2S; and increased plasma homocysteine level. However, histological examinations of liver did not reveal any abnormality and plasma levels of aspartate aminotransferase, alanine aminotransferase, and albumin were normal in these animals. No CSE-KO mice survived after 12 weeks of feeding with the cysteine-limited diet. Supplementation of H2S to the CSE-KO mice failed to reverse the aforementioned abnormalities. On the other hand, supplementation of cysteine in the drinking water of the CSE-KO mice significantly increased plasma cysteine and glutathione levels. This eventually led to an increase in body weight and rescued the animals from death. In conclusion, CSE is critical for cysteine biosynthesis through the transsulfuration pathway and the combination of CSE deficiency and lack of dietary cysteine supply would threaten life sustainability. 相似文献
73.
Microspheres of tramadol hydrochloride (TM) for oral delivery were prepared by complex coacervation method without the use
of chemical cross-linking agents such as glutaraldehyde to avoid the toxic reactions and other undesirable effects of the
chemical cross-linking agents. Alternatively, ionotropic gelation was employed by using sodium-tripolyphosphate as cross-linking
agent. Chitosan and gelatin B were used as polymer and copolymer, respectively. All the prepared microspheres were subjected
to various physicochemical studies, such as drug–polymer compatibility by thin layer chromatography (TLC) and Fourier transform
infrared (FTIR) spectroscopy, surface morphology by scanning electron microscopy, frequency distribution, drug entrapment
efficiency, in vitro drug release characteristics and release kinetics. The physical state of drug in the microspheres was determined by differential
scanning calorimetry (DSC) and X-ray diffractometry (XRD). TLC and FTIR studies indicated no drug–polymer incompatibility.
All the microspheres showed initial burst release followed by a fickian diffusion mechanism. DSC and XRD analysis indicated
that the TM trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. From
the preliminary trials, it was observed that it may be possible to formulate TM microspheres by using biodegradable natural
polymers such as chitosan and gelatin B to overcome the drawbacks of TM and to increase the patient compliance. 相似文献
74.
Background
Role of immune system in protecting the host from cancer is well established. Growing cancer however subverts immune response towards Th2 type and escape from antitumor mechanism of the host. Activation of both innate and Th1 type response is crucial for host antitumor activity. In our previous study it was found, that Mycobacterium indicus pranii (MIP) also known as M. w induces Th1 type response and activates macrophages in animal model of tuberculosis. Hence, we studied the immunotherapeutic potential of MIP in mouse tumor model and the underlying mechanisms for its antitumor activity.Methodology and Principal Findings
Tumors were implanted by injecting B16F10 melanoma cells subcutaneously into C57BL/6 mice. Using the optimized dose and treatment regimes, anti-tumor efficacy of heat killed MIP was evaluated. In MIP treated group, tumor appeared in only 50–60% of mice, tumor growth was delayed and tumor volume was less as compared to control. MIP mediated immune activation was analysed in the tumor microenvironment, tumor draining lymph node and spleen. Induction of Th1 response and higher infiltration of immune cells in the tumor microenvironment was observed in MIP treated mice. A large fraction of these immune cells were in activated state as confirmed by phenotypic and functional analysis. Interestingly, percentage of Treg cells in the tumor milieu of treated mice was less. We also evaluated efficacy of MIP along with chemotherapy and found a better response as compared to chemotherapy alone.Conclusion
MIP therapy is effective in protecting mice from tumor. It activates the immune cells, increases their infiltration in tumor, and abrogates tumor mediated immune suppression. 相似文献75.
Mani I Hu Z Jang SB Samuel K Krause M Phillips J Wu CH 《Comparative and Functional Genomics》2005,6(1-2):72-76
Interest in information extraction from the biomedical literature is motivated by the need to speed up the creation of structured databases representing the latest scientific knowledge about specific objects, such as proteins and genes. This paper addresses the issue of a lack of standard definition of the problem of protein name tagging. We describe the lessons learned in developing a set of guidelines and present the first set of inter-coder results, viewed as an upper bound on system performance. Problems coders face include: (a) the ambiguity of names that can refer to either genes or proteins; (b) the difficulty of getting the exact extents of long protein names; and (c) the complexity of the guidelines. These problems have been addressed in two ways: (a) defining the tagging targets as protein named entities used in the literature to describe proteins or protein-associated or -related objects, such as domains, pathways, expression or genes, and (b) using two types of tags, protein tags and long-form tags, with the latter being used to optionally extend the boundaries of the protein tag when the name boundary is difficult to determine. Inter-coder consistency across three annotators on protein tags on 300 MEDLINE abstracts is 0.868 F-measure. The guidelines and annotated datasets, along with automatic tools, are available for research use. 相似文献
76.
Alikhani Z Alikhani M Boyd CM Nagao K Trackman PC Graves DT 《The Journal of biological chemistry》2005,280(13):12087-12095
Both aging and diabetes are characterized by the formation of advanced glycation end products (AGEs). Both exhibit other similarities including deficits in wound healing that are associated with higher rates of fibroblast apoptosis. In order to investigate a potential mechanism for enhanced fibroblast apoptosis in diabetes and aged individuals, experiments were carried out to determine whether the predominant advanced glycation end product in skin, N-epsilon-(carboxymethyl) lysine (CML)-collagen, could induce fibroblast apoptosis. In vivo experiments established that CML-collagen but not unmodified collagen induced fibroblast apoptosis and that apoptosis was dependent upon caspase-3, -8, and -9 activity. In vitro experiments demonstrated that CML-collagen but not control collagen induced a time- and dose-dependent increase in fibroblast apoptosis. By use of blocking antibodies, apoptosis was shown to be mediated through receptor for AGE signaling. AGE-induced apoptosis was largely dependent on the effector caspase, caspase-3, which was activated through both cytoplasmic (caspase-8-dependent) and mitochondrial (caspase-9) pathways. CML-collagen had a global effect of enhancing mRNA levels of pro-apoptotic genes that included several classes of molecules including ligands, receptors, adaptor molecules, mitochondrial proteins, and others. However, the pattern of expression was not identical to the pattern of apoptotic genes induced by tumor necrosis factor alpha. 相似文献
77.
Bhushan D Pandey A Chattopadhyay A Choudhary MK Chakraborty S Datta A Chakraborty N 《Journal of proteome research》2006,5(7):1711-1720
The extracellular matrix (ECM) or cell wall is a dynamic system and serves as the first line mediator in cell signaling to perceive and transmit extra- and intercellular signals in many pathways. Although ECM is a conserved compartment ubiquitously present throughout evolution, a compositional variation does exist among different organisms. ECM proteins account for 10% of the ECM mass, however, comprise several hundreds of different molecules with diverse functions. To understand the function of ECM proteins, we have developed the cell wall proteome of a crop legume, chickpea (Cicer arietinum). This comprehensive overview of the proteome would provide a basis for future comparative proteomic efforts for this important crop. Proteomic analyses revealed new ECM proteins of unknown functions vis-à-vis the presence of many known cell wall proteins. In addition, we report here evidence for the presence of unexpected proteins with known biochemical activities, which have never been associated with ECM. 相似文献
78.
79.
80.
Pierre Neuvial Philippe Hupé Isabel Brito Stéphane Liva élodie Manié Caroline Brennetot Fran?ois Radvanyi Alain Aurias Emmanuel Barillot 《BMC bioinformatics》2006,7(1):264