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911.
In all cell types, protein homeostasis, or “proteostasis,” is maintained by sophisticated quality control networks that regulate protein synthesis, folding, trafficking, aggregation, disaggregation, and degradation. In one notable example, Escherichia coli employ a proteostasis system that determines whether substrates of the twin-arginine translocation (Tat) pathway are correctly folded and thus suitable for transport across the tightly sealed cytoplasmic membrane. Herein, we review growing evidence that the Tat translocase itself discriminates folded proteins from those that are misfolded and/or aggregated, preferentially exporting only the former. Genetic suppressors that inactivate this mechanism have recently been isolated and provide direct evidence for the participation of the Tat translocase in structural proofreading of its protein substrates. We also discuss how this discriminatory “folding sensor” has been exploited for the discovery of structural probes (e.g., sequence mutations, pharmacologic chaperones, intracellular antibodies) that modulate the folding and solubility of virtually any protein-of-interest, including those associated with aggregation diseases (e.g., α-synuclein, amyloid-β protein). Taken together, these studies highlight the utility of engineered bacteria for rapidly and inexpensively uncovering potent anti-aggregation factors. 相似文献
912.
《Cell》2021,184(23):5699-5714.e11
913.
N. Jacobs Roland Greimers Alessandra Mazzoni Mohamed Trebak Nicole Schaaf-Lafontaine Jacques Boniver Michel P. Moutschen 《Cancer immunology, immunotherapy : CII》1996,42(6):369-375
In this study we have specifically investigated the participation of T cells in the cytotoxic activity of peripheral blood
lymphocytes (PBL) activated by interleukin-2 (IL-2, 50 U/ml) alone or in combination with an anti-CD3 mAb (BMA030, 10 ng/ml,
IgG2a). Purified CD3+ T cells, incubated in the presence of the anti-CD3 mAb for 4 days, mediated a cytotoxic activity against HL60 and U937 tumor
cell lines. Several findings suggested the involvement of a redirected-cytotoxicity phenomenon, since the lytic process was
restricted to target cell lines bearing the high-affinity Fcγ receptor (FcγRI) and T lymphocytes stimulated by IL-2 alone
did not lyse these cell lines. Furthermore, anti-CD3 mAb F(ab′)2, anti-CD3 IgG1 (UCHT1), phytohemagglutinin or staphylococcal enterotoxin A did not induce a similar cytotoxic activity in
T lymphocytes. The cytotoxic process occurred in the presence of a very low level of anti-CD3 antibodies (in the nanomolar
range). The cytotoxic activity of T cells stimulated by IL-2 or by IL-2 + BMA030, against OVCAR-3 cells (MOv18+ ovarian tumor cell line), was also compared in the presence of a bispecific antibody (OC/TR, anti-CD3 × MOv18). The stimulation
by IL-2 + BMA030 induced approximately a twofold higher cytotoxic activity than IL-2-activated T cells. This could be related
to the state of activation of effector cells stimulated by IL-2 + BMA030, since the phenotypic analysis showed an increased
proportion of T cells expressing several activation/differentiation markers (CD25, HLA-DR, CD45R0, adhesion molecules). These
findings could be applied to the design of therapeutic protocols using anti-CD3 ×antitumoral bispecific antibodies.
Received: 6 December 1995 / Accepted: 4 June 1996 相似文献
914.
Ken Igarashi Jun’ichi Oda Yuzo Inouye Minoru Ohno 《Bioscience, biotechnology, and biochemistry》2013,77(5):811-812
About 30 dipeptides and some tripeptides were led to new benzimidazole derivatives by incorporating their carboxyl groups into benzimidazole ring by the reaction with o-phenylenediamine. The ring closure to benzimidazole was well achieved by heating mildly at a moderate temperature in acetic acid.Some benzimidazole derivatives of peptides had remarkable phytotoxicities. 相似文献
915.
《Bioscience, biotechnology, and biochemistry》2013,77(9):1788-1793
The results of our previous in vitro study indicated that the intensity of the Ca2+ signal could determine T cell activation and anergy. We show here that the T cell response of mice that had been treated with cyclosporine A during oral tolerance induction was higher than that of control mice, indicating that the Ca2+ signal could also determine T cell activation and tolerization in vivo. However, T cell activation was not apparent at any concentration of ionomycin, although a low dose of anti-CD3 monoclonal antibody (mAb) induced activation, while a high dose induced anergy in vitro. These results indicate that the balance between the Ca2+ signal and other signals which can also be induced by anti-CD3 stimulation, but not the actual intensity of the Ca2+ signal or the presence of co-stimulation, played an important role in regulating T cell activation and anergy. 相似文献
916.
A calmodulin acceptor protein has been identified in isolated hamster caudal sperm by immunofluoresence and Western transfer techniques. The protein shows a localization in sperm heads identical to calmodulin. Fluorescence of both calmodulin and the acceptor protein are lost by treatment with MgCl2, conditions which release the acrosome. These results are consistent with the proposed function of calmodulin in a sperm function. 相似文献
917.
Wanwisa Dejnirattisai Daming Zhou Helen M. Ginn Helen M.E. Duyvesteyn Piyada Supasa James Brett Case Yuguang Zhao Thomas S. Walter Alexander J. Mentzer Chang Liu Beibei Wang Guido C. Paesen Jose Slon-Campos César López-Camacho Natasha M. Kafai Adam L. Bailey Rita E. Chen Baoling Ying Gavin R. Screaton 《Cell》2021,184(8):2183-2200.e22
918.
Julie Chao Lee Chao Harry S. Margolius 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,801(2):244-249
Rat spleen kallikrein was identified and purified by DEAE-cellulose and monoclonal antibody-affinity chromatography. The purified enzyme has Tos-Arg-OMe esterase activity and kinin-releasing activity from a purified low-molecular-weight kininogen substrate. In the direct radioimmunoassay for tissue kallikrein, the splenic enzyme displays parallelism with standard curves of rat urinary kallikrein. The pH profiles of the Tos-Arg-OMe esterase activities of spleen and urinary kallikrein were identical with optima at 9.0 Rat spleen kallikrein was inhibited strongly by aprotinin and affinity-purified kallikrein antibody and weakly by soybean trypsin inhibitor. The IC50 values were similar to those observed against rat urinary kallikrein. Neither the urinary nor the splenic enzyme was inhibited by lima bean trypsin inhibitor or preimmune serum immunoglobulins. Spleen kallikrein was labeled with [14]diisopropylphosphorofluoridate and visualized by fluorography on a sodium dodecyl sulfate-polyacrylamide gel. The electrophoretic mobility of the splenic enzyme was indistinguishable from that of urinary kallikrein A with an estimated Mr of approx. 38 000. With Western blot analyses using a rabbit anti-kallikrein antibody followed by 125I-labeled protein A binding, the spleen and urinary kallikreins were again visualized at identical positions by autoradiography. The data show that there is a rat splenic tissue kallikrein which is indistinguishable from a renal kallikrein with respect to physicochemical properties, immunological character and susceptibility to inhibitors. 相似文献
919.
《Cell》2021,184(22):5593-5607.e18
920.
Monoclonal antibodies used as probes for the structural organization of the central region of fibronectin 总被引:6,自引:0,他引:6
Two monoclonal mouse antibodies against human plasma fibronectin were compared in their reactivity for proteolytic fragments of the antigen by enzyme immunoassay and immunoblotting. These antibodies were shown to react with two different structures within a short segment (about 30 kDa) located about one-third away from the C-terminus of the fibronectin chains. 相似文献