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The structure of the hexameric L-alanine dehydrogenase from Phormidium lapideum reveals that the subunit is constructed from two domains, each having the common dinucleotide binding fold. Despite there being no sequence similarity, the fold of alanine dehydrogenase is closely related to that of the family of D-2-hydroxyacid dehydrogenases, with a similar location of the active site, suggesting that these enzymes are related by divergent evolution. L-alanine dehydrogenase and the 2-hydroxyacid dehydrogenases also use equivalent functional groups to promote substrate recognition and catalysis. However, they are arranged differently on the enzyme surface, which has the effect of directing opposite faces of the keto acid to the dinucleotide in each case, forcing a change in absolute configuration of the product. 相似文献
155.
KP Ober 《Canadian Metallurgical Quarterly》1997,126(2):157-163
Dopamine has been implicated in the function of a diverse set of central nervous system and peripheral functions. We theoretically evaluated the chemistry of interaction between dopamine and its receptor using ab initio molecular orbital calculation. First, we calculated the total energy of dopamine on either a protonated or deprotonated molecule at the meta- or para-position hydroxy group of the catechol ring, and then evaluated the hydrogen bond effect in these hydroxy groups. These results suggested that the meta-position hydroxy group was liable to be protonated, and subsequently deprotonated by a negatively charged receptor site. It was considered that proton flopping, which occurred within the receptor site via the meta-position hydroxy group, appeared to be essential for exerting the biological action of dopamine. On the other hand, the para-position hydroxy group of the catechol ring contributed to stabilization of a dopamine molecule at the receptor site through a hydrogen bond. Second, we showed that the side-chain amino group of dopamine was readily protonated and bound a negatively charged receptor site by coulomb interaction. Third, we calculated the highest occupied molecular orbital and lowest unoccupied molecular orbital to elucidate chemical reactivities of these functional groups on the electron level. From the molecular orbital contour maps, it was suggested that frontier orbital interaction was involved in the dopamine-receptor interaction, in which the meta- and para-position hydroxy groups may function as a proton acceptor and a proton donor, respectively. Considering these theoretical results together, we hereby propose a model of the dopamine-receptor interaction: (1) a protonation-deprotonation at the meta-position hydroxy group takes place, (2) the protonated side-chain amino group of dopamine binds to a negatively charged receptor site by an ionic bond, and (3) the para-position hydroxy group not only contributes to stabilization for dopamine binding but may also enhance the protonation-deprotonation at the meta-position through bond interaction along the pi-bond between OH and the benzene ring. 相似文献
156.
DG Skinner JB Dekernion PA Brower KP Ramming YH Pilch 《Canadian Metallurgical Quarterly》1976,115(3):246-250
Herein we describe the first clinical treatment of renal cell carcinoma in humans with xenogeneic immune ribonucleic acid. Twelve patients with advanced renal cell carcinoma have been treated by appropriate operations to remove tumor bulk followed by specific passive immunotherapy. Xenogeneic specific immune ribonucleic acid was prepared from the spleen of normal sheep that had received 4 weekly injections of a homogenate of renal cell carcinoma. Results indicate that 1) xenogeneic specific immune ribonucleic acid can safely be given to humans without local or systemic toxicity, 2) there is a suggestion of clinical benefit, since only 2 patients have had progression of known metastases during treatment with immune ribonucleic acid and 3) xenogeneic immune ribonucleic acid can enhance the immune response to renal cell carcinoma, as demonstrated by in vitro lymphocytoxicity tests. 相似文献
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It is common to examine the cerebrospinal fluid in untreated or inadequately treated asymptomatic patients with a reactive serum fluorescent treponemal antibody absorption (FTA-ABS) test before initiating antibiotic therapy for syphilis. This prospective study evaluated the usefulness of such examination. Four hundred thirty-two patients over 40 years old, reporting for annual physical examination, had a serum FTA-ABS test. Thirty-seven (8.6%) patients and 2 of 4 spouses were reactive repeatedly. Of the 39 patients with reactive tests, 7 had a history of penicillin therapy for syphilis, 5 had received heavy metal therapy, and 27 had no history of syphilis. These 39 patients had a neurological examination, serum VDRL, Treponema pallidum immobilization (TPI), and repeat FTA-ABS tests by two other laboratories. The TPI test was reactive in 30 (77%). Four had nonspecific neurological signs. Routine CSF examination (cells, total protein, VDRL, glucose, IgG%) on 30 patients with a history of inadequate treatment had a low diagnostic yield. Two patients had an unexplained total protein elevation (57 and 61 mg/dl) and 1 had a mildly increased IgG% (15%). All cell counts, VDRL tests, and glucose levels were normal. Agarose electrophoresis demonstrated one or more CSF immunoglobulin bands in 10 (36%) of 28 patients, possibly representing an immunological marker of past or latent central nervous system infection. 相似文献
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Twenty-five patients with metastatic renal cell carcinoma and ten patients with minimum residual disease, but at high risk of recurrence after surgery, received weekly intradermal injections of purified RNA extracted from lymphoid organs of sheep immunized with human renal cell carcinoma. A retrospective control group consisted of 86 consecutive patients with metastatic renal cell carcinoma from the same institution. Group survival was notable in RNA-treated patients who had multiple metastases limited to the lungs when compared with matched controls. Therapy did not influence the survival of patients with metastases to other sites or with multiple organ involvement. Eight of ten patients with minimum residual disease remained free of recurrence from 16 to 36 months after the initiation of therapy. Toxicity of RNA therapy was minimal. Changes in skin test response to dinitrochlorobenzene and common antigens, and levels of lymphocyte-mediated cytotoxicity and complement-fixing antibody, were primarily related to changes in tumor burden. Immune RNA therapy may be of value in selected patients with metastatic renal cell carcinoma and as adjunctive therapy after definitive surgery. 相似文献